Management of advanced breast cancer

Summary guidance from NICE suggests (1):

Diagnosis and assessment Imaging assessment

• assessment to the presence and extent of visceral metastases
  • using a combination of plain radiography, ultrasound, computed tomography (CT) scans and magnetic resonance imaging (MRI)
• assess the presence and extent of metastases in the bones of the axial skeleton
  • using bone windows on a CT scan or MRI or bone scintigraphy
• assess proximal limb bones for the risk of pathological fracture in patients with evidence of bone metastases elsewhere
  • using bone scintigraphy and/or plain radiography
• MRI to assess bony metastases if other imaging is equivocal for metastatic disease or if more information is needed (for example, if there are lytic metastases encroaching on the spinal canal)
• Positron emission tomography fused with computed tomography (PET-CT)
  • should only be used to make a new diagnosis of metastases for patients with breast cancer whose imaging is suspicious but not diagnostic of metastatic disease

Pathological assessment

• oestrogen receptor status
  • patients with tumours of known oestrogen receptor (ER) status whose disease recurs should not have a further biopsy just to reassess ER status
• human epidermal growth factor receptor 2 status
  • patients with tumours of known human epidermal growth factor receptor 2 (HER2) status whose disease recurs should not have a further biopsy just to reassess HER2 status
• assess ER and HER2 status at the time of disease recurrence if receptor status was not assessed at the time of initial diagnosis. In the absence of tumour tissue from the primary tumour, and if feasible, obtain a biopsy of a metastasis to assess ER and HER2 status.

Systemic therapy:

• endocrine therapy is first-line treatment for the majority of patients with ER-positive advanced breast cancer
• chemotherapy should be offered as first-line treatment for patients with ER positive advanced breast cancer whose disease is imminently life-threatening or requires early relief of symptoms because of significant visceral organ involvement, providing they understand and are prepared to accept the toxicity
• for patients with ER-positive advanced breast cancer who have been treated with chemotherapy as their first-line treatment, endocrine therapy should be offered following the completion of chemotherapy
• endocrine therapy
  • an aromatase inhibitor (either non-steroidal or steroidal) should be offered to:
    • postmenopausal women with ER-positive breast cancer and no prior history of endocrine therapy
    • postmenopausal women with ER-positive breast cancer previously treated with tamoxifen.
  • tamoxifen and ovarian suppression is first-line treatment to premenopausal and perimenopausal women with ER-positive advanced breast cancer not previously treated with tamoxifen
  • ovarian suppression should be offered to premenopausal and perimenopausal women who have previously been treated with tamoxifen and then experience disease progression
  • tamoxifen is first-line treatment to men with ER-positive advanced breast cancer
• chemotherapy
  • on disease progression, systemic sequential therapy should be offered to the majority of patients with advanced breast cancer who have decided to be treated with chemotherapy
  • combination chemotherapy should be considered to treat patients with advanced breast cancer for whom a greater probability of response is important and who understand and are likely to tolerate the additional toxicity
  • for patients with advanced breast cancer who are not suitable for anthracyclines (because they are contraindicated or because of prior anthracycline treatment either in the adjuvant or metastatic setting), systemic chemotherapy should be offered in the following sequence:
    • first line: single-agent docetaxel
    • second line: single-agent vinorelbine or capecitabine
    • third line: single-agent capecitabine or vinorelbine (whichever was not used as second-line treatment)
  • gemcitabine in combination with paclitaxel, within its licensed indication, is recommended as an option for the treatment of metastatic breast cancer only when docetaxel monotherapy or docetaxel plus capecitabine are also considered appropriate
• biological therapy
  • for patients who are receiving treatment with trastuzumab for advanced breast cancer
    • discontinue treatment with trastuzumab at the time of disease progression outside the central nervous system
    • do not discontinue trastuzumab if disease progression is within the central nervous system alone ((1)
    • trastuzumab emtansine (T-DM1), an antibody–drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy (3)
    • NICE state that Trastuzumab emtansine is recommended as an option for the adjuvant treatment of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer in adults who have residual invasive disease in the breast or lymph nodes after neoadjuvant taxane-based and HER2-targeted therapy (4)

For more detailed guidance then consult the full guidelines.

Reference:

• 1. NICE (March 2017). Advanced breast cancer Diagnosis and treatment
• 2. NICE (June 2012). Lapatinib or trastuzumab in combination with an aromatase inhibitor for the first-line treatment of metastatic hormonereceptor- positive breast cancer that overexpresses HER2
• 3. Minckwitz G et al.Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med 2019 Feb 14;380(7):617-628
• 4. NICE (June 2020). Trastuzumab emtansine for adjuvant treatment of HER2-positive early breast cancer