Hormone Positive Metastatic Breast Cancer

Scottish Cancer Network: Clinical Management Pathways
NHS National Services Scotland
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The treatment of metastatic breast cancer (MBC) will differ for every patient with no single pathway determined as “best practice”.  This pathway lists the treatments available for MBC in Scotland with guidance to support joint decision making with the patient.  The choice and availability of therapy is determined by first diagnosis of metastatic disease or recurrence, previous treatment and response to prior therapies, general health, liver/renal/bone marrow function, sites of disease and access to clinical trials.  Initial doses and frequency are suggested but should be adjusted to take into account individual patient factors in line with the relevant SACT protocol.

 

CDK4/6 Inhibitors

CDK4/6 inhibitors are effective in de novo or recurrent MBC and are indicated for treatment in combination with endocrine therapy.  The side effect profiles of CDK4/6 inhibitors differ, patients who develop severe toxicity to a CDK4/6 inhibitor may tolerate an alternative.

First line use of endocrine therapy as monotherapy followed by combination therapy with a CDK4/6 inhibitor second line may be considered where there is patient preference for this approach. Further evidence is needed before this approach can be considered standard for all patients.  

Endocrine therapy alone should be considered for patients with contraindications or poor performance status precluding the use of CDK4/6 inhibitors or patient preference.
Pre- and perimenopausal women must receive ovarian function suppression (OFS) in addition to all endocrine-based therapies.​ 

CDK 4/6 inhibitor in combination with endocrine therapy plus OFS if indicated

Ribociclib 600mg orally once daily on days 1-21 every 28 days (First line only)

In combination with an aromatase inhibitor, for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer as initial endocrine-based therapy.

Abemaciclib 150mg orally twice daily continuously

Treatment of women with HR positive, HER2 negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy, or in women who have received prior endocrine therapy.

Treatment of women with HR positive, HER2 negative locally advanced or metastatic breast cancer in combination with fulvestrant as initial endocrine-based therapy or in women who have received prior endocrine therapy.

SMC restriction: for use in women who have progressed on or after (neo) adjuvant endocrine therapy, or progressed during first-line endocrine-based therapy for advanced breast cancer

Palbociclib 125mg orally once daily on days 1-21 every 28 days 

Treatment of hormone receptor HR positive, HER2 negative locally advanced or metastatic breast cancer:

- in combination with an aromatase inhibitor;
- in combination with fulvestrant in women who have received prior endocrine therapy.

Aromatase inhibitors (AI)

  • Letrozole 2.5mg orally once daily continuously
  • Exemestane 25mg orally once daily continuously
  • Anastrozole 1mg orally once daily continuously

Ovarian Function Suppression (OFS)

  • Leuprorelin 3.75mg s/c every 28 days or 11.25mg s/c every 3 months
  • Triptorelin 3mg s/c every 28 days
  • Goserelin 3.6mg s/c every 28 days or 10.8mg every 12 weeks

Endocrine Therapy

Endocrine therapy alone should be considered for patients with contraindications or poor performance status precluding the use of CDK4/6 inhibitors or for patient preference.  First line use of endocrine therapy as monotherapy followed by combination therapy with a CDK4/6 inhibitor second line may also be considered where there is patient preference for this approach. Further evidence is needed before this approach can be considered standard for all patients. 

The optimal sequence of endocrine-based therapy in metastatic setting is uncertain after progression on CDK4/6 inhibitors and depends on previous treatment, duration of response to previous endocrine therapy, disease burden, patient preference and treatment availability.​ In general, patients with an initial good response to endocrine therapy should continue with second line endocrine-based therapy; patients with rapid progression should be considered for chemotherapy with or without maintenance endocrine monotherapy and OFS if indicated.

Pre- and perimenopausal women should receive ovarian function suppression (OFS) in addition to all endocrine-based therapies.​

Endocrine Therapy: Monotherapy/in combination with Chemotherapy

  • Letrozole 2.5mg orally once daily continuously
  • Anastrozole 1mg orally once daily continuously
  • Exemestane 25mg orally once daily continuously
  • Fulvestrant 500mg IM days 1 & 14 of cycle 1 then every 28 days
  • Tamoxifen 20mg orally once daily continuously

Endocrine Therapy in combination with selective mTOR inhibitor

Exemestane 25mg and Everolimus 5-10mg orally once daily continuously until disease progression/toxicity

Palliative SACT Regimens

Sequential single-agent treatment is generally preferred but combination therapy should be considered if a rapid response is needed.  The optimal sequence of therapy in MBC has not been established. Available options should be discussed with the patient as part of shared decision making consultation.  The following treatments are not listed in order; restrictions to line of therapy are specified for each.

Anthracyline based treatment

Epirubicin 60mg/m2  and cyclophosphamide 600mg/m2 IV  3-weekly for up to 6 cycles.

Epirubicin 30mg/m2 IV weekly until 12 weeks then move to 2 weekly maintenance until toxicity or disease progression.  (If proceeding with treatment beyond maximum cumulative dose of 900mg/m2 the patient should be consulted and re-consented.)

Taxanes

Paclitaxel 80mg/m2  IV weekly for up to 12-18 weeks then reduce to 2 weekly until toxicity or disease progression.

Docetaxel 75-80mg/m2  IV 3-weekly for up to 6 cycles.

Capecitabine

Capecitabine 1000mg/m2 PO bd d1-14 3-weekly. Continue until progression or toxicity.

Vinorelbine

Vinorelbine 60-80 mg/m2 oral days 1+8, or 25mg/m2 IV 3-weekly.

Cyclophosphamide

Cyclophosphamide 50mg orally once a day continuously until toxicity/progression.

Trastuzumab deruxtecan (HER2-low only)

HER2-low status is defined as tumours scoring 2+ or 1+ by IHC and no evidence of HER2 gene amplification.
Trastuzumab deruxtecan 5.4 mg/kg every 3 weeks until disease progression/toxicity.
  • SMC 2608 for unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing (neo)adjuvant chemotherapy.

Eribulin

Eribulin 1.23mg/m2  IV on day 1 and 8 of a 21-day cycle continued until progression or toxicity

  • SMC 1065/15 in progressive disease after at least two prior chemotherapeutic regimens for advanced disease which includes capecitabine if indicated.

PARP Inhibitors

PARP inhibitor monotherapy can be considered for patients with germline pathogenic BRCA1/2 mutations who have received previous treatment with endocrine therapy, anthracycline/taxane.

TALAZOPARIB

Talazoparib 1mg orally once daily until disease progression/unacceptable toxicity

As monotherapy for the treatment of adult patients with germline BRCA1/2 mutations, who have HER2-negative locally advanced or metastatic breast cancer. Patients should have been previously treated with an anthracycline and/or a taxane in the (neo)adjuvant, locally advanced or metastatic setting unless patients were not suitable for these treatments. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine-based therapy or considered unsuitable for endocrine-based therapy.

References

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Editorial Information

Last reviewed: 27/03/2024

Next review date: 27/03/2027

Author(s): Lisa MacLeod.

Version: 1.1

Reviewer name(s): Frances Yuille.