Since breast cancer is most likely a generalised disease, a generalised treatment regimen must also be used.
Systemic neoadjuvant and adjuvant therapy is an integral part of the treatment of breast cancer patients and, alongside surgical tumour removal, contributes significantly to reducing mortality. Before systemic therapy is carried out, the patient’s general condition must be assessed and adherence estimated. Treatment decisions have become very complex today because of extended diagnostic and treatment options.
The patient’s individual risk assessment is based on clinicopathological criteria such as tumour size, lymph node status and molecular predictors of the tumour’s biological behaviour. Targeted therapies against HER2 and third-generation aromatase inhibitors provide new treatment options that must be integrated into modern treatment algorithms. Because of the heterogeneity of metastases and individual disease courses, no uniform treatment strategy can be prescribed. This applies in particular to cytotoxic treatment of metastatic breast cancer.
Although monotherapy has lower remission rates than combination chemotherapy, survival time is not significantly affected. Monotherapies are better tolerated, so they should be used whenever possible. Combination chemotherapy is indicated only in the case of severe symptoms, rapid tumour growth and aggressive tumour behaviour.
Before and during chemotherapy, the patient’s general condition must be examined and assessed. During treatment, the degree of toxicity must be determined regularly. The treatment effect should be evaluated at least every 3 months. In the event of progression or marked toxicity, treatment should be discontinued.
The therapeutic index (individual patient benefit vs. treatment-related side effects) should be positive in the overall assessment of treatment.
Modern neoadjuvant and adjuvant systemic therapy is now based on individualised risk profiles and, in addition to classic chemotherapy, includes above all endocrine treatment options and immunological treatment approaches. Endocrine therapy is the treatment of choice when hormone receptor status is positive. Endocrine therapy is less toxic than chemotherapy and should therefore generally be used as first-line therapy. With a positive hormone receptor status, remission can be expected in 60% of patients; with a negative hormone receptor status, in <10%.
If a patient responds to endocrine therapy, it is continued until progression.
In postmenopausal patients with metastatic disease, after adjuvant therapy with tamoxifen or no hormone therapy, the first endocrine treatment step is the use of an aromatase inhibitor. Further steps in the endocrine treatment cascade in postmenopausal patients, depending on prior anti-hormonal treatment, are the use of anti-oestrogens, oestrogen receptor antagonists, high-dose progestogens or switching from a steroidal to a non-steroidal aromatase inhibitor or vice versa.
In premenopausal patients, suppression of ovarian function (GnRH analogues, oophorectomy, ovarian irradiation) in combination with tamoxifen is the treatment of first choice. Subsequently, ovarian suppression in combination with an aromatase inhibitor can be used in premenopausal women. A further step is treatment with high-dose progestogens.
Neoadjuvant (primary, preoperative) systemic therapy is now regarded as standard treatment for patients with locally advanced, primarily inoperable or inflammatory breast cancer within a multimodal treatment concept. Neoadjuvant chemotherapy is an alternative treatment option for women in whom mastectomy is indicated but who want breast-conserving surgery. The effect is greatest in hormone receptor-negative cancers. Resection within the new tumour margins is possible if an R0 resection with an adequate safety margin can thereby be achieved. Primary hormone therapy is an option for postmenopausal patients with receptor-positive tumours in whom surgery is contraindicated or who decline surgery. Patients with involved axillary lymph nodes should receive adjuvant combination therapy with taxanes.
Adjuvant endocrine therapy (following chemotherapy) with positive hormone receptor status (ER-positive and/or PgR-positive)
- Premenopausal:
– Tamoxifen for 5 years or
– Goserelin for 2–3 years and tamoxifen for 5 years
- Postmenopausal:
– Tamoxifen for 5 years (low-risk patients only)
– Aromatase inhibitor (e.g. anastrozole, letrozole) for 5 years
– Alternatively: after 2–3 years of tamoxifen, switch to an aromatase inhibitor (e.g. exemestane, anastrozole)
– Alternatively: extended adjuvant endocrine therapy: after 5 years of tamoxifen, a further 2–5 years of an aromatase inhibitor (e.g. letrozole)
The St. Gallen consensus conferences have developed risk stratification based on prognostic parameters such as primary tumour size, nodal status, hormone receptor status, HER2/neu expression and histological features (Goldhirsch et al. 2005, 2007)
These treatment recommendations focus not on recurrence risk but on therapeutic targets such as hormone receptor status and HER2/neu expression (Löhrs and Bauerfeind 2007). Traditional clinicopathological criteria such as lymph node status, size of the primary tumour and histological grading are now supplemented in risk assessment by biological and molecular markers such as the hormone receptors [oestrogen (ER+) and progesterone receptor (PR+)], the HER2/neu receptor, gene expression patterns and histological features.
Modern neoadjuvant and adjuvant systemic therapy of breast cancer is based on the patient’s individualised risk profile, which takes histopathological and clinical criteria into account. Hormone sensitivity is an important treatment-relevant characteristic of tumours. In most patients, systemic therapy can be given before or after surgery with equal effectiveness. Multimodal concepts incorporating cytotoxic and anti-hormonal regimens and immunological therapy with trastuzumab are used in various combinations.
This results in an indication for HER2 inhibitors in HER2-overexpressing tumours in combination with chemotherapy or as monotherapy after prior treatment with taxanes and anthracyclines. When paclitaxel is used as first-line cytotoxic therapy for metastatic breast cancer, bevacizumab (a VEGF inhibitor) can be used to inhibit angiogenesis in order to improve treatment success, thereby prolonging the time to disease progression.
A promising treatment approach is the use of bisphosphonates in the primary treatment of breast cancer in premenopausal and postmenopausal patients (Gnant et al. 2009). Bisphosphonates are used as standard in the treatment of skeletal metastases and recently also appear to have a protective effect in other areas. In particular, zoledronic acid in combination with chemotherapy in early breast cancer can significantly reduce the risk of local and distant metastases.
