ADVANCED/METASTATIC BREAST CANCER

Recommendations

Strength of the recommendation

Diagnosis, pathology and molecular biology

At first diagnosis of MBC, a biopsy should be carried out to confirm histology and assess/re-assess tumour biology including ER, PgR, HER2 status & KI 67.

Strong

Staging and risk assessment

The minimum imaging work-up for staging includes computed tomography (CT) of the chest and abdomen, and bone scintigraphy.

Strong

18F-FDG-PET)/CT may be used instead of CT and bone scans only as problem solving tool.

 Conditional

 The interval between imaging and starting treatment should be ≤4 weeks.

Good practice statement.

Evaluation of response should generally occur every 2-4 months depending on disease dynamics, location, extent of metastasis and type of treatment.

Good practice statement.

Disease monitoring intervals should not be shortened as there is no evidence of an OS benefit but potential for emotional and financial harm. Less frequent monitoring is acceptable, particularly for indolent disease.

Good practice statement.

If progression is suspected, additional tests should be carried out in a timely manner irrespective of planned intervals.

Good practice statement.

Repeat bone scans are a mainstay of evaluation for bone-only/predominant metastases, but image interpretation may be confounded by a possible flare during the first few months of treatment. MRI may be added to define response in specific locations.

 Conditional

 Impending fracture risk should be evaluated by CT or X-rays. In the case of suspected cord compression, MRI is the modality of choice.

Strong

Symptomatic patients should always undergo brain imaging, preferably with MRI.

Strong

HR-positive, HER2-negative breast cancer

First Line.

A CDK4/6 inhibitor combined with endocrine therapy (ET) may be used as first-line therapy for patients with ER-positive, HER2-negative MBC. However this depends  on the availability, access-ability, patient comorbidity, and budget impact.

Conditional

Pre- and perimenopausal women should be offered OFS or ovarian ablation in addition to all endocrine-based therapies.

Strong

Second-line treatment.

Selection of second-line therapy (chemotherapy versus further endocrine-based therapy) should be based on disease aggressiveness, extent and organ function, and consideration of the associated toxicity profile.

Good practice statement.

Everolimus- exemestane is a recommended option.

Strong

Tamoxifen or fulvestrant can also be combined with everolimus and is recommended. If everolimus is used, stomatitis prophylaxis must be used.

Strong

At least two lines of endocrine-based therapy are preferred before moving to chemotherapy in the absence of endocrine refractory disease and/or imminent organ failure.

Strong

 In patients with imminent organ failure, chemotherapy is the preferred option.

Strong

For patients with endocrine-sensitive tumours, continuation of ET with agents not previously received in the metastatic setting is recommended.

Strong

Beyond second-line treatment

Patients with tumours that are endocrine resistant should be considered for chemotherapy.

Strong

Sequential single-agent chemotherapy is generally preferred over combination strategies. In patients where a rapid response is needed due to imminent organ failure, combination chemotherapy is preferred.

Strong

Available drugs for single-agent chemotherapy include anthracyclines, taxanes, capecitabine, vinorelbine, and platinums.

Strong

HER2-positive breast cancer

Standard first-line treatment of HER2-positive MBC should be trastuzumab-docetaxel regardless of HR status.

Strong

Docetaxel should be given for at least six cycles, if tolerated, followed by maintenance trastuzumab until progression.

Strong

An alternative taxane (paclitaxel) can be substituted for docetaxel.

Strong

ET can be added to trastuzumab maintenance after completion of chemotherapy for HER2-positive, HR-positive .

Strong

If chemotherapy is contraindicated in patients with HER2-positive, HR-negative MBC, HER2-targeted therapy without chemotherapy (e.g. trastuzumab) is recommended.

Strong

if taxane chemotherapy is contraindicated, a less toxic chemotherapy partner (e.g. capecitabine or vinorelbine) should be considered.

Strong

In selected cases of HER2-positive, HR-positive MBC where the patient is not suitable for first-line chemotherapy, ET (e.g. an AI) in combination with an HER2-targeted therapy, such as trastuzumab, or lapatinib, can be recommended.

Strong

The use of single-agent ET without HER2-targeted therapy in HER2-positive, HR-positive MBC is not routinely recommended unless comorbidities (e.g. cardiac disease) preclude the safe use of HER2-directed therapies.

Conditional

 Patients with metastatic recurrence within 12 months of receiving adjuvant trastuzumab should follow the second-line therapy recommendations.

Strong

In later lines of therapy, lapatinib is an evidence-based therapy option to be used preferably in combinations (e.g. with capecitabine, trastuzumab or ET).

Conditional

TNBC

In cases of imminent organ failure, combination therapy is preferred based on a taxane and/or anthracycline combination.

After progression, all chemotherapy recommendations for HER2-negative disease also apply for TNBC, e.g. capecitabine, and vinorelbine.

Site-specific management

Primary stage IV disease

For patients with newly diagnosed stage IV breast cancer and an intact primary tumour, therapeutic decisions should ideally be discussed in a multidisciplinary context.

Good practice statement.

Locoregional treatment of the primary tumour in the absence of symptomatic local disease does not lead to an OS benefit and is not routinely recommended.

Good practice statement.

 In patients with local symptoms caused by the primary tumour or metastatic disease, the use of local treatment modalities should be evaluated.

Strong

Surgery of the primary tumour is recommended for patients who may benefit from salvage surgery (e.g. those with bone-only metastases, a good response to initial systemic therapy, HR-positive tumours, HER2-negative tumours, age <55 years and those with OMD).

Strong

Surgery or RT of the primary tumour should be carefully considered for circumstances in which they provide added value for symptom palliation or prevention of complications.

Conditional

Oligometastatic disease

A multidisciplinary approach is essential to manage patients with bone metastases and prevent skeletal-related events (SREs).

Good practice statement.

Patients with OMD should be discussed in a multidisciplinary context to individualise management.

Good practice statement.

Multimodality treatment approaches involving locoregional therapy [e.g. high conformal radiotherapy (RT), image-guided ablation,selective internal RT and/or surgery] combined with systemic treatments are recommended, and should be tailored to the disease presentation in the individual patient.

Strong

Local ablative therapy to all metastatic lesions may be offered on an individual basis after discussion in a multidisciplinary setting.

Conditional

Bone metastases and bone-modifying agents

A multidisciplinary approach is essential to manage patients with bone metastases and prevent skeletal-related events (SREs).

Strong

 An orthopaedic evaluation is advised in the case of significant lesions in the long bones or vertebrae as well as in patients with MSCC to discuss the possible role of surgery.

Strong

RT is recommended for lesions at moderate risk of fracture and those associated with moderate to severe pain.

Strong

A single 8-Gy RT fraction is as effective as fractionated schemes in patients with uncomplicated bone metastases.

Strong

RT should be delivered after surgery for stabilisation or separation surgery for MSCC.

Strong

Bone-modifying agents (BMAs) are recommended for patients with bone metastases,regardless of symptoms.

Strong

Before the initiation of BMAs, patients should have a complete dental evaluation and ideally complete any required dental treatment. Calcium and vitamin D supplements should be prescribed.

Strong

 The optimal duration of BMA therapy has not been defined but it is reasonable to interrupt therapy after 2 years for patients in remission.

Good Practice Statement

The ideal sequence of therapies has not been defined but it seems reasonable to document tumour response with a systemic treatment before suggesting locoregional therapy.

Conditional

Brain metastases and leptomeningeal metastases

Brain metastases should be managed according to the recommendations outlined in the European Association of Neuro-Oncology-ESMO (EANO-ESMO) Clinical Practice Guideline (CPG) for the management of patients with brain metastases from solid tumours.

Strong

Leptomeningeal metastases should be treated according to the recommendations outlined in the EANO-ESMO CPG for the management of patients with leptomeningeal metastases from solid tumours.

Strong

Long-term implications and survivorship

An interdisciplinary approach is critical, including specialised oncology and/or breast care nurses to proactively screen for and manage treatment-emergent toxicities.

Good practice statement.

Patients should be informed about treatment choices and side-effect profiles of recommended systemic treatments.

Good practice statement.

All treatments should include formal patient education regarding side-effects of  management.

Strong

All efforts should be done to encourage integrated electronic medical records (EMR) in different hospitals.

Strong

QoL assessments should be incorporated into the evaluation of treatment efficacy.

Strong

Dose reduction and delay are effective strategies to manage toxicity in advanced disease.

Strong