St Gallen and the National Comprehensive CancerNetwork Guidelines

Every year experts in the field of oncology gather in St. Gallen, Switzerland, and provide guidelines based on available evidence for the therapy of early-stage breast cancer. In the most recent publication,1 Stemming from the 2007 St. Gallen conference, patients were divided into three different risk categories:

1.  Low risk: lymph node-negative patient with grade 1 tumor, tumor size less than 2 cm, absence of vascular invasion, estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive lesion, HER2/neu-negative status, age greater than 35 years

2.  Intermediate risk: lymph node-negative patient who does not fit in low risk or who is lymph node-positive and ER and/or PR positive, HER2/ neu-negative status

3.  High risk: any lymph node-positive patient who does not fit in the intermediate category

Treatment recommendations depend on the risk category of the patient. More specifically, in low-risk patients, endocrine therapy is recommended. In intermediate-risk patients, endocrine therapy remains the treatment of choice for the endocrine-responsive patients, although chemotherapy can be considered. For individuals who are HER2-positive, trastuzumab is included in the recommendations. Finally, in high-risk patients, chemotherapy is recommended in all patients with endocrine therapy, and trastuzumab is offered for endocrine-responsive and HER2-positive disease, respectively. Furthermore, the use of neoadjuvant chemotherapy was considered by the majority of the panel members in cases in which it would improve resectability, whereas a minority of the panel members considered the assessment of responsiveness a reason to use this treatment.

Another set of guidelines that influence physicians all around the world comes from the National Comprehensive Cancer Network (NCCN).2 A total of 26 experts from centers in the United States publish guidelines every year based on data from clinical trials. These treatment guidelines are similar to the St. Gallen guidelines, although they divide patients into stages based on the TNM system. The use of gene-expression profiles such as Oncotype DX and MammaPrint are recommended by the panel to aid in treatment decisions. In general, these guidelines are meant to help the physician formulate treatment recommendations. However, individual patients merit individual decision making, and therefore a candid discussion with the patient is an irreplaceable tool.

Early Breast Cancer Trialists' Collaborative Group Systematic Review on Polychemotherapy (Oxford Overview)

Since the initiation of the first randomized trials of adjuvant therapy, several prospective randomized clinical trials comparing adjuvant chemotherapy with placebo have been conducted and reported. Most trials compare local therapy with or without the addition of systemic chemotherapy. The trials vary by type of agent investigated, treatment duration, and number of agents. Because individual trials may yield different results as a result of statistical and other biases, attempts have been made to perform systematic reviews of multiple studies that examined similar questions. The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) has met every 5 years since the mid-1980s to perform a systematic review of all randomized clinical trials that have been performed in early-stage breast cancer. Early metaanalyses have focused on cyclophosphamide, methotrexate, 5-fluorouracil (CMF)-like and anthracycline-like regimens, showing the superiority of receiving adjuvant therapy versus no treatment. Currently, the most recent publication on the systematic review of polychemotherapy for early breast cancer is from the 2005 overview.3 This review includes 194 randomized trials in early breast cancer of almost 150,000 women. With a 15-year follow-up, chemotherapy offered a significant benefit in both recurrence-free survival (RFS) and breast cancer mortality in women younger than 50 years of age (12.3% 15-year benefit in RFS, standard error [SE] 1.6, P < 0.00001; 10% benefit in mortality, SE 1.6, P < 0.00001). For women older than 50 years of age, the benefit although significant, was not as high (4.1% 15-year benefit in RFS, SE 1.2, P < 0.00001; 30% relative benefit in mortality, SE 1.3, P < 0.00001). This benefit remained significant regardless of the axillary lymph node status. The benefit from adjuvant chemotherapy was higher in ER-poor disease compared with ER-positive disease but remained significant in both subgroups of patients. In women younger than 50 years of age with ER-poor disease, the 5-year benefit from chemotherapy was 13.2% (SE 2.4, P < 0.00001), whereas the benefit in the same population with ER-positive disease was 7.6% (SE 1.7, P < 0.00001). Similarly in women 50 to 69 years of age with ER-poor disease, the 5-year benefit from chemotherapy was 9.6% (SE 1.8, P < 0.00001), whereas the benefit in the same population with ER-positive disease was 4.9% (SE 0.9; P < 0.00001).

Recently, results from the EBCTCG were published focusing on the role of chemotherapy in ER-poor breast cancer.4 The meta-analysis included 96 trials and about 20,000 women with ER-poor breast cancer. The meta-analysis showed that adjuvant chemotherapy significantly reduced the risk of recurrence, breast cancer mortality, as well as overall mortality in women. More specifically, in women younger than 50 years of age, there was a 15% absolute benefit (hazard ratio [HR] 0.73, P = 0.0002) in RFS and an 8% absolute benefit (HR 0.75, P = 0.0003) in mortality. In women between 50 and 69 years of age, the absolute benefit in RFS with the use of chemotherapy was 10% (HR 0.82, P < 0.00001) and in mortality 6% (HR 0.87, P = 0.0009).

Adjuvant Chemotherapy

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  • Category: Women's diseases