Breast cancer rarely occurs in women below the age of 35 years. Data from various sources indicate that diagnosis at such an age is associated with a dire prognosis mainly because of a more ...aggressive presentation. Although the effect of chemotherapy for premenopausal patients is substantial, recent evidence on 2233 patients suggested that very young women with endocrine-responsive tumors had a statistically significantly higher risk of relapse than older premenopausal patients with such tumors. In contrast, results for younger and older premenopausal patients were similar if their tumors were classified as endocrine nonresponsive. Information from studies on 7631 patients who were treated with chemotherapy alone in trials of three major U.S. cooperative groups showed a similar interaction between the effect of age and steroid hormone receptor status of the primary tumor. Better treatments for very young patients are required and may involve ovarian function suppression in addition to other endocrine agents in patients with endocrine responsive tumors and a more precise investigation of chemotherapy and its timing, duration, and intensity in those with endocrine nonresponsive tumors. Very young women with this disease are faced with personal, family, professional, and quality-of-life issues, which further complicate the phase of treatment decision making. The development of more effective therapies for younger patients requires tailored treatment investigations and cannot rely on information predominantly contributed from older premenopausal women.
Introduction International Breast Cancer Study Group (IBCSG) Trial 11-93 is the largest trial evaluating the role of the addition of chemotherapy to ovarian function suppression/ablation (OFS) and ...tamoxifen in premenopausal patients with endocrine-responsive early breast cancer. Methods IBCSG Trial 11-93 is a randomized trial comparing four cycles of adjuvant chemotherapy (AC: doxorubicin or epirubicin, plus cyclophosphamide) added to OFS and 5 years of tamoxifen versus OFS and tamoxifen without chemotherapy in premenopausal patients with node-positive, endocrine-responsive early breast cancer. There were 174 patients randomized from May 1993 to November 1998. The trial was closed before the target accrual was reached due to low accrual rate. Results Patients randomized tended to have lower risk node-positive disease and the median age was 45. After 10 years median follow up, there remains no difference between the two randomized treatment groups for disease-free (hazard ratio = 1.02 (0.57-1.83); P = 0.94) or overall survival (hazard ratio = 0.97 (0.44-2.16); P = 0.94). Conclusion This trial, although small, offers no evidence that AC chemotherapy provides additional disease control for premenopausal patients with lower-risk node-positive endocrine-responsive breast cancer who receive adequate adjuvant endocrine therapy. A large trial is needed to determine whether chemotherapy adds benefit to endocrine therapy for this population.
Patients with endocrine-responsive breast cancer represent a distinct population for which tailored adjuvant treatments are needed. Endocrine therapy is mandatory for this population. For ...premenopausal patients, ovarian ablation or tamoxifen can be recommended; the combination of both, as well as the combination of ovarian ablation and aromatase inhibitors is under investigation. For postmenopausal patients, tamoxifen for 5 years is the ‘standard of care’. Anastrozole can be recommended for patients with a contraindication to tamoxifen. The addition of 5 years of letrozole after 5 years of tamoxifen has yielded benefits in terms of disease-free survival. The sequential use of tamoxifen and exemestane was superior to tamoxifen for 5 years. However, in both studies, long-term toxicity is still not fully evaluated. The addition of chemotherapy to endocrine treatment can be recommended for patients at high risk of relapse and in young patients. Chemotherapy should consist of 3–6 cycles of cyclophosphamide, methotrexate, 5-fluorouracil or of an anthracycline-containing regimen. The addition of taxanes cannot be routinely recommended in this population. Endocrine treatment should start after completion of chemotherapy.
To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast ...Cancer Study Group (IBCSG) Trials VII and 12–93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (
P
= 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (
P
= 0.07), or for the cohort with one positive node (
P
= 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high.
Why did the study fail? Dellapasqua, Silvia; Castiglione-Gertsch, Monica
European journal of cancer (1990),
12/2005, Letnik:
41, Številka:
18
Journal Article
To compare adjuvant dose-intensive epirubicin and cyclophosphamide chemotherapy administered with filgrastim and progenitor cell support (DI-EC) with standard-dose anthracycline-based chemotherapy ...(SD-CT) for patients with early-stage breast cancer and a high risk of relapse, defined as stage II disease with 10 or more positive axillary nodes; or an estrogen receptor-negative or stage III tumor with five or more positive axillary nodes.
Three hundred forty-four patients were randomized after surgery to receive seven cycles of SD-CT over 22 weeks, or three cycles of DI-EC (epirubicin 200 mg/m2 plus cyclophosphamide 4 gm/m2 with filgrastim and progenitor cell support) over 6 weeks. All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS).
After a median follow-up of 5.8 years (range, 3 to 8.4 years), 188 DFS events had occurred (DI-EC, 86 events; SD-CT, 102 events). The 5-year DFS was 52% for DI-EC and 43% for SD-CT, with hazard ratio of DI-EC compared with SD-CT of 0.77 (95% CI, 0.58 to 1.02; P = .07). The 5-year overall survival was 70% for DI-EC and 61% for SD-CT, with a hazard ratio of 0.79 (95% CI, 0.56 to 1.11; P = .17). There were eight cases (5%) of anthracycline-induced cardiomyopathy (two fatal) among those who received DI-EC. Women with hormone receptor-positive tumors benefited significantly from DI-EC.
There was a trend in favor of DI-EC with respect to disease-free survival. A larger trial or meta-analysis will be required to reveal the true effect of dose-intensive therapy.
Obesity is associated with different cancers including breast cancer, whose incidence is increased in postmenopausal women. It has an adverse impact on the prognosis of the patients, regardless of ...their menopausal status. The fact of receiving a systemic adjuvant therapy does not neutralize the prognostic role of obesity. Moderate weight loss after cancer diagnosis could improve the outcome of the patients, while a weight gain during treatment seems without significant effect. Currently available data are still too incomplete to justify systematic programs to lose weight with an oncologic therapeutic aim. However, it is worth to encourage and support our patients to have an optimal diet, physical activity, and to lose weight as promotion of general health.
Hormonal manipulations have been used for more than 100 years for the treatment of metastatic breast cancer and after definition of the concept of micro-metastases also in the adjuvant setting. In ...the postmenopausal population, tamoxifen has played the most important role for almost four decades. Progestins or the first generation of aromatase inhibitors (AIs) were only marginally used in the adjuvant setting due to their prohibitive toxicity. The new generation of anti-estrogen compounds, the selective estrogen receptor down-regulators (SERDs) like fulvestrant have a higher affinity for the estrogen receptor than tamoxifen, but none of its agonist activities, and have shown promising clinical activity in the treatment of advanced breast cancer. The third generation of AIs investigated in six large trials has been reported to be superior to tamoxifen in terms of disease-free survival, but not in terms of survival. These trials will be discussed in terms of results in different subpopulations and of toxicity.
Abstract Purpose To develop a Risk Score (RS) to predict distant recurrence among premenopausal women with node-negative endocrine-responsive early breast cancer. Methods The Cox model was used to ...develop the RS using clinical and histopathological features from 378 women participating in the IBCSG Trial VIII who received endocrine therapy alone or following chemotherapy. The performance of the resulting model was validated on a cohort of 1005 patients from a single institution who received endocrine therapy alone. Results In a multivariable analysis, the risk of distant recurrence was associated with tumor size, ER, Ki-67 and peritumoral vascular invasion. In the validation cohort, patients with high RS were at greater risk of distant recurrence compared to patients with low RS (HR, 17.41; 95% CI, 5.72–52.95). Conclusion In premenopausal women with node-negative endocrine-responsive early breast cancer, the RS identifies patients at higher risk of distant recurrence.
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