Systemic adjuvant therapy includes all forms of hormonal manipulation (known as endocrine therapy) and/or antineoplastic agents administered in conjunction with local therapy for breast cancer. The aim of such therapy in early breast cancer is to treat undetectable remaining cancer, which will reduce the risk of clinically evident metastatic disease and local recurrence.13 For some women, use of targeted therapy is also indicated. The goals of treatment in advanced breast cancer are to maximise overall survival and quality of life.38
Systemic treatment recommendations in the adjuvant setting for breast cancer are based on several factors, these include:13
- risk of cancer recurring
- nodal status
- survival benefit versus risk of potential adverse side effects of adjuvant therapies
- oestrogen and progesterone receptor status
- menopausal status
- willingness to undergo treatment.
Clinical guidelines recommend the use of moderately prolonged (several months) combination treatment for early stage breast cancer. Evidence supports the use of anthracycline-containing regimens which are superior to the older regimen of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) for both recurrence-free survival and overall survival. However, it is acknowledged that there is increased risk of alopecia, cardiac toxicity and neutropenia.13
Dose intensity is important to outcomes for women affected by breast cancer. Higher doses (not requiring colony stimulating factor support) achieve more effective results than lower doses.13
The use of taxanes is becoming common, with improved disease-free and overall survival reported with their use. A taxane-containing regimen is considered for women at intermediate-to-high risk of breast cancer recurrence, taking into consideration her individual risk profile and co-morbidities.36
Agents used to treat advanced breast cancer include:38
- alkylating agents, e.g. cyclophosphamide
- anthracyclines, e.g. doxorubicin, epirubicin
- antimetabolites, e.g. capecitabine, 5-fluorouracil, gemcitabine, methotrexate
- taxanes, e.g. docetaxel, paclitaxel, nab-paclitaxel
The action of endocrine therapy is to inhibit the growth of breast cancer cells which are hormone receptor positive. Endocrine therapies include:33
- ovarian suppression/ablation, e.g. luteinising hormone-releasing hormone agonists (goserelin, buserelin), ovarian irradiation, and surgical oophorectomy
- anti-oestrogens or selective oestrogen receptor modulators, e.g. tamoxifen. Tamoxifen is recommended for most women with oestrogen receptor positive tumours, as it significantly improves recurrence-free and overall survival in women of all age groups. Tamoxifen reduces the incidence of contralateral breast cancer10
- selective oestrogen downregulators, e.g. fulvestrant
- progestins, .e.g. megestrol acetate and medroxyprogesterone
- aromatase inhibitors, e.g. anastrozole, letrozole, and exemestane, which block the conversion of androgens to oestrogen. They are only effective for women who have gone through menopause.39 Adjuvant endocrine therapy with an aromatase inhibitor significantly improved disease-free survival in post-menopausal women with hormone receptor-positive early breast cancer compared with tamoxifen or placebo.31
Side effects of hormonal therapies include hot flushes, vaginal dryness, and reduced libido.33 Tamoxifen can also be associated with venous thrombosis, stroke, cancer of the uterus, and changes in vision.33 Additional side effects of aromatase inhibitors include bone pain, arthralgia, and osteoporosis.31
Trastuzumab (Herceptin) is a monoclonal antibody which targets breast cancer cells that over-express the HER2 protein. This protein is present in approximately 20% of newly diagnosed breast cancers. In women with HER2-positive early, advanced or metastatic breast cancer, the addition of adjuvant trastuzumab to adjuvant antineoplastic therapy improves disease-free, overall survival and/or disease progression.32 Side effects of trastuzumab include increased risk of cardiac dysfunction. Long-term effects are not known.
Bevacizumab and lapatinib are also used to treat advanced breast cancer.38
Discuss the nursing implications associated with administration of anthracycline- based toxic drugs.
Explain the term 'dose intensity' and the implications of sub-optimal dose intensity in the management of breast cancer.
Compare aromatase inhibitors and anti-oestrogen therapies in the management of breast cancer on the following criteria:
- Indications for use (tumour related factors and menopausal status)
- Side effects.
Explain why trastuzumab (Herceptin) is considered a targeted therapy.
Identify the key toxicities associated with trastuzumab and explain inventions for prevention, early detection, and management of these effects.
Systemic treatment protocol
M ☐ F ☑
5-FU 500mg/m2 IV D1
Epirubicin 100mg/m2 IV D1
Cyclophosphamide 500 mg/m2 IV D1
Followed by Anastrozole 1mg/day orally
Libby's story 5: systemic therapies
Discuss the implications of Libby's previous treatment for breast cancer in determining her current treatment.
For each of the drugs in Libby's treatment protocol, describe the:
- classification of the drug
- common toxicities associated with the drug
- nursing interventions for prevention, early detection, and management of these toxicities
- other nursing considerations associated with administering these agents.
Outline the differences between tamoxifen and anastrozole and discuss the indication of each in Libby's disease management.
Discuss how an SCN would prepare Libby and Samantha for Libby's first course of therapy in an ambulatory care setting?
Outline the service capability requirements for a rural or remote facility that would ensure an individual such as Libby could safely receive her adjuvant systemic therapies closer to home if she chose.
If you were the SCN working in the major tertiary hospital, how would you provide support to a satellite regional centre administrating Libby's therapy?