medical oncology/ Master Degree - breast cancer treatment

Adjuvant therapy

The oestrogen receptor (ER) status of all invasive breast cancers should be assessed, using immunohistochemistry with a standardised and qualitatively assured methodology and the result reported quantitatively. The progesterone receptor status of tumours in patients with invasive breast cancer should not be reported routinely but will be available where it is considered that it will influence the patient management. The human epidermal growth receptor 2 (HER2) status of all invasive breast cancers should be assessed, using a standardised and qualitatively assured methodology, in all patients under 75 years of age. It should be ensured that the results of ER (+/- PR) and HER2 assessments be available and recorded at the MDT meeting when decisions about systemic treatment are made. Adjuvant therapy planning Adjuvant therapy should be considered at the MDT meeting for all patients and the decisions recorded in the patient’s notes. Decisions should be made based on assessment of the prognostic and predictive factors and the potential benefits and side effects of the treatment. Decisions should be made following discussion of these factors with the patient. Consideration should be given to using Adjuvant Online for patients with early invasive breast cancer to support estimations of individual prognosis and the absolute benefit of any proposed adjuvant treatment. Adjuvant chemotherapy or radiotherapy should be started as soon as clinically possible and certainly within 31 days of completion of surgery. Radiotherapy Radiotherapy after breast conserving surgery Patients with early invasive breast cancer who have had breast conserving surgery with clear margins should have breast radiotherapy. Adjuvant radiotherapy should be discussed with patients with high-grade DCIS following adequate breast conserving surgery and the potential benefits and risks explained. Following breast conserving surgery, postoperative radiotherapy to the intact breast should be delivered via a tangent pair. Standard dose will be 40 Gy in 15 fractions. In large volume breasts, consideration should be given to treatment with 50 Gy in 25 fractions. An external beam boost to the site of local excision should be considered in patients with early invasive breast cancer who are at high risk of local recurrence, following breast conserving surgery with clear margins and whole breast radiotherapy. If an external beam boost to the site of local excision is being considered, the patient should be informed of the side effects associated with this intervention, including poor cosmesis, particularly in women with larger breasts. Boost with electron beam or brachytherapy implant to tumour bed should be at the discretion of the treating clinician depending on age, pathology, margin status and menopausal status of the patient. Radiotherapy after mastectomy Adjuvant chest wall radiotherapy should be given to patients with early invasive breast cancer who have had a mastectomy and are at a high risk of local recurrence. Patients at a high risk of local recurrence include those with tumours more than 5 cm in diameter, four or more positive axillary lymph nodes or close / involved resection margins.Consideration should be given to entering patients who have had a mastectomy for early invasive breast cancer and who are at an intermediate risk of local recurrence into the current UK trial (SUPREMO) assessing the value of postoperative radiotherapy. Patients at an intermediate risk of local recurrence include those with less than 3 nodes involved, lymphovascular invasion, histological grade 3 tumours, ER-negative tumours, and those aged under 40. Radiotherapy should not be given following mastectomy to patients with early invasive breast cancer who are at low risk of local recurrence Radiotherapy doses of 40 Gy in 15 fractions or 50 Gy in 25 fractions via tangent pair to chest wall or direct electron beam therapy to chest wall should be given Radiotherapy for DCIS Patients with low or intermediate grade disease with adequate surgical margins may avoid radiotherapy. The potential benefits and risks of radiotherapy should be discussed with all patients with high grade disease. Following mastectomy, there is no established role for postoperative radiotherapy. Radiotherapy to nodal areas Adjuvant radiotherapy to the axilla should not be offered to patients with early breast cancer who have been shown to be histologically lymph node-negative. Adjuvant radiotherapy should not be given to the axilla after axillary lymph node dissection. If axillary lymph node dissection is declined following a positive axillary SLNB or four-node sample, adjuvant radiotherapy to the axilla should be considered. Adjuvant radiotherapy to the axilla and supraclavicular fossa should be given to patients with early breast cancer post axillary sampling when four or more axillary lymph nodes are involved or there is macroscopic evidence of residual disease in the axilla. It should also be considered for patients with early breast cancer and one to three positive lymph nodes if they have other poor prognostic factors and good performance status. Adjuvant radiotherapy to the supraclavicular fossa alone should be after axillary node clearance when the highest node is involved or four or more lymph nodes are involved. Adjuvant radiotherapy to the internal mammary chain should not be given to patients with early breast cancer who have had breast surgery. Consent forms should document the increased risk of lymphoedema post axillary surgery with subsequent radiotherapy. The doses to be used should be 40 Gy in 15 fractions or 50 Gy in 25 fractions direct field using asymmetric technique to match the tangent pair used for the chest wall or intact breast. Endocrine therapy Women with ER positive tumours will benefit from at least 5 years of anti-oestrogen therapy. All patients with ER positive disease should, therefore, receive endocrine therapy. Following results of the ATLAS and ATTom trials, ASCO guidelines published June 2014 recommend extended adjuvant endocrine therapy for women with early breast cancer either with tamoxifen alone or using sequential treatment with tamoxifen and aromatase inhibitors, with the exception being those women treated with aromatase inhibitors for 5 years as there is currently a paucity of data to support the use of aromatase inhibitors beyond 5 years Patients with hormone receptor negative disease should not receive endocrine therapy. If the patient is receiving adjuvant chemotherapy, endocrine therapy should be deferred until chemotherapy has finished. Any vaginal bleeding whilst on tamoxifen should be investigated by a gynaecologist. Pre-menopausal patients There is good evidence that adjuvant tamoxifen works in pre-menopausal women. All premenopausal women should receive at least 5 years of tamoxifen 20 mg once a day. Treatment beyond 5 years can be with either tamoxifen or an aromatase inhibitor dependent on menopausal status. There is no evidence that ovarian ablation should be used in addition to tamoxifen unless tamoxifen is not tolerated, there is a desire by the patient to avoid menstruation or there are problems with compliance. Postmenopausal patients Postmenopausal women with ER positive early invasive breast cancer who are not considered to be at low risk (NPI >3.4), should be offered an aromatase inhibitor, either anastrozole or letrozole, as their initial adjuvant therapy. Tamoxifen should be offered to women at low risk and also if an aromatase inhibitor is not tolerated or contraindicated. The choice of treatment should be made after discussion between the responsible clinician and the patient about the risks and benefits of each option. The aromatase inhibitors anastrozole, exemestane and letrozole, within their licensed indications, are recommended as options for the adjuvant treatment of early ER-positive invasive breast cancer in postmenopausal women. Therapy should be continued for at least 5 years. Treatment options beyond 5 years include, tamoxifen for 10 years or switching to an aromatase inhibitor for extended therapy. An aromatase inhibitor, either exemestane or anastrozole should be offered, instead of tamoxifen to postmenopausal women with ER positive early invasive breast cancer who are not at low risk and who have been treated with tamoxifen for 2–3 years. Factors to consider when making the choice include whether the woman has received tamoxifen before, the licensed indications and side-effect profiles of the individual drugs and, in particular, the assessed risk of recurrence. All aromatase inhibitors increase the risk of osteoporosis and its complications. Therefore, all patients who receive an aromatase inhibitor should be advised regarding the implications for osteoporosis. Concerns regarding bone density should not prevent the prescription of aromatase inhibitors. All women who have finished chemotherapy and who are commencing treatment with an aromatase inhibitor should have a baseline dual energy X-ray absorptiometry (DEXA) scan. Lifestyle advice should be given to help reduce the risk of osteoporosis such as regular weight bearing exercise, cessation of smoking and a high calcium diet. Ovarian suppression for early invasive breast cancer Ovarian suppression / ablation should be offered using gosarelin 3.6 mg subcutaneously once monthly for 2 years in addition to tamoxifen in pre-menopausal women with ER positive early invasive breast cancer who have been offered chemotherapy but have chosen not to have it. It should also be considered in premenopausal women who are unable to tolerate tamoxifen. Chemotherapy The Arden Cancer Network Breast NSSG has agreed to adopt the NCNN breast cancer chemotherapy guidelines with local addenda. Clinical trial entry will be encouraged which may necessitate variation from the standard treatment regimes. Standard adjuvant chemotherapy regime options include: • FEC x 6 cycles o Fluorouracil 600mg/m2 o Epirubicin 75 mg/m2 o Cyclophosphamide 600mg/m2 • AC x 4 cycles o Doxorubicin 60 mg/m2 o Cyclophosphamide 600 mg/m2 • FEC – T x 6 cycles o Fluorouracil 500mg/m2 o Epirubicin 100mg/m2 o Cyclophosphamide 500mg/m2 x 3 cycles, o Followed by Docetaxel 100mg/m2 x 3 cycles Where an anthracycline is contraindicated regime options include: • CMF x 6 cycles o Cyclophosphamide 600mg/m2, o Methotrexate 40mg/m2 o Fluorouracil 600mg/m2 • Docetaxel/Cyclophosphamide x 4 cycles o Docetaxel 75mg/m2 o Cyclophosphamide 600mg/m2 All node positive patients considered for adjuvant chemotherapy should be offered a taxane containing regime, most commonly FEC – T. Neo-adjuvant chemotherapy The decision to offer neo-adjuvant chemotherapy should be made at the MDT and decision regarding the extent of likely definitive surgery should be considered at that juncture. Breast conserving surgery following neo-adjuvant chemotherapy can be considered. Based on the following factors • Size of the tumour • Focality of the tumour • Position of the tumour within the breast • ER and HER2 receptor status The data available from randomised trials shows that breast conserving surgery after neoadjuvant chemotherapy is associated with a increased risk of local recurrence. When neoadjuvant chemotherapy is being considered with a view to breast conserving surgery, the increased risk of local recurrence should be discussed with the patient. The majority of inflammatory cancers will be treated with neo-adjuvant chemotherapy, definitive mastectomy followed by postoperative radiotherapy. Pre-operative/neo-adjuvant chemotherapy regime options include: • FEC x 6 – reassess at 3-4 cycles. o Fluorouracil 600mg/m2 o Epirubicin 75 mg/m2 o Cyclophosphamide 600mg/m2 FEC-T (+/-Trastuzumab) x 6 cycles o Fluorouracil 500mg/m2 o Epirubicin 100mg/m2 o Cyclophosphamide 500mg/m2 x 3 cycles o Followed by Docetaxel 100mg/m2 x 3 cycles • TC (+/-Trastuzumab) x 6 cycles o Docetaxel 75mg/m2 o Carboplatin AUC 6 Biological therapy When applicable, trastuzumab (Herceptin) should be given at 3-week intervals for one year or until disease recurrence (whichever is the shorter period), as an adjuvant treatment to women with HER2-positive early invasive breast cancer following surgery, chemotherapy, and radiotherapy. An assessment of cardiac function should be made before starting treatment with trastuzumab and it should not be offered to women who have any of the following: • a left ventricular ejection fraction (LVEF) of 55% or lessa history of documented congestive heart failure • high-risk uncontrolled arrhythmias • angina pectoris requiring medication • clinically significant valvular disease • evidence of transmural infarction on electrocardiograph (ECG) • poorly controlled hypertension Repeat cardiac functional assessments should be made every three months during trastuzumab treatment. If the LVEF drops by 10 % (ejection) points or more from baseline and to below 50%, then trastuzumab treatment should be suspended. Trastuzumab therapy should only be restarted after further cardiac assessment and a fully informed discussion of the risks and benefits with the woman. The standard protocol is a loading dose of 8mg/kg followed by 6mg/kg repeated three weekly to a total of 17 doses.