Systemic Treatment of Patients with Metastatic Breast Cancer
Publication Date: January 8, 2024
Last Updated: January 10, 2024
Treatment
Table 3. First-Line Systemic Metastatic Breast Cancer Treatment
A. In Basic settings, the recommendations presume that neither chemotherapy, nor targeted therapy or molecular testing are available.
Italics = medications on Essential Medicines List (EML) (not universally available in low-income and lower-middle-income countries [<50%])
Italics, Underlined = not on EML
B. Per the “Palliative Care in the Global Setting: ASCO Resource-Stratified Guideline" Recommendations: There should be a coordinated system where the palliative care needs of patients and families are identified and met at all levels, in collaboration with the team providing oncology care. The health care system should have trained personnel who are licensed to prescribe, deliver, and dispense opioids at all levels. Distance communication should be instituted at the national or regional level through oncology centers (or other tertiary care centers) to support those providing oncology care to patients in lower resource areas.
C. General: Palliative care needs should be addressed for all patients with cancer at presentation using appropriate screening, especially when disease-modifying interventions are not available.
D. Patients eligible for PARPi if they previously received chemotherapy for neoadjuvant, adjuvant, or metastatic disease.
* Palliative care may or may not include radiation therapy for symptom control.
** For patients who are pre-menopausal: can only receive aromatase inhibitors if accompanied by ovarian ablation or ovarian suppression
Italics = medications on Essential Medicines List (EML) (not universally available in low-income and lower-middle-income countries [<50%])
Italics, Underlined = not on EML
B. Per the “Palliative Care in the Global Setting: ASCO Resource-Stratified Guideline" Recommendations: There should be a coordinated system where the palliative care needs of patients and families are identified and met at all levels, in collaboration with the team providing oncology care. The health care system should have trained personnel who are licensed to prescribe, deliver, and dispense opioids at all levels. Distance communication should be instituted at the national or regional level through oncology centers (or other tertiary care centers) to support those providing oncology care to patients in lower resource areas.
C. General: Palliative care needs should be addressed for all patients with cancer at presentation using appropriate screening, especially when disease-modifying interventions are not available.
D. Patients eligible for PARPi if they previously received chemotherapy for neoadjuvant, adjuvant, or metastatic disease.
* Palliative care may or may not include radiation therapy for symptom control.
** For patients who are pre-menopausal: can only receive aromatase inhibitors if accompanied by ovarian ablation or ovarian suppression
HR-Positive, HER2-Negative
1.1.1
Population
HR-positive, HER2-negative
Post-menopausal
HR-positive, HER2-negative
Post-menopausal
Basic
Tamoxifen, palliative,* and best supportive care should be provided.
Surgery and tamoxifen when patient presents with certain symptoms (, , , )
Tamoxifen, palliative,* and best supportive care should be provided.
Surgery and tamoxifen when patient presents with certain symptoms (, , , )
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Limited
Sequential hormone therapy**
Aromatase inhibitors (AIs) only if ovarian ablation/ovarian suppression (OA/OS) is available** (, , , )
Sequential hormone therapy**
Aromatase inhibitors (AIs) only if ovarian ablation/ovarian suppression (OA/OS) is available** (, , , )
1048203
Enhanced
Sequential hormone therapy** (, , , )
Sequential hormone therapy** (, , , )
1048203
1.1.2
Population
HR-positive, HER2-negative with immediately life-threatening disease or in those with rapid visceral recurrence on adjuvant hormone therapy
HR-positive, HER2-negative with immediately life-threatening disease or in those with rapid visceral recurrence on adjuvant hormone therapy
Basic
Tamoxifen
Palliative* and best supportive care (, , , )
Tamoxifen
Palliative* and best supportive care (, , , )
1048203
Limited
Single-agent chemotherapy
Combination regimens may be offered for symptomatic or immediately life-threatening disease (, , , )
Single-agent chemotherapy
Combination regimens may be offered for symptomatic or immediately life-threatening disease (, , , )
1048203
Enhanced
Single-agent chemotherapy
Combination regimens may be offered for symptomatic or immediately life-threatening disease (, , , )
Single-agent chemotherapy
Combination regimens may be offered for symptomatic or immediately life-threatening disease (, , , )
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1.1.3
Population
HR-positive, HER2-negative with immediately life-threatening disease without (w/o) prior adjuvant hormone therapy
HR-positive, HER2-negative with immediately life-threatening disease without (w/o) prior adjuvant hormone therapy
Basic
Tamoxifen
Palliative* and best supportive care (, , , )
Tamoxifen
Palliative* and best supportive care (, , , )
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Limited
Single-agent chemotherapy
Combination regimens may be offered for symptomatic or immediately life-threatening disease (, , , )
Single-agent chemotherapy
Combination regimens may be offered for symptomatic or immediately life-threatening disease (, , , )
1048203
Enhanced
Single-agent chemotherapy
Combination regimens may be offered for symptomatic or immediately life-threatening disease for which time may allow only one potential chance for therapy (, , , )
Single-agent chemotherapy
Combination regimens may be offered for symptomatic or immediately life-threatening disease for which time may allow only one potential chance for therapy (, , , )
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1.1.4
Population
HR-positive, HER2-negative
Post-menopausal w/o prior adjuvant hormone therapy
HR-positive, HER2-negative
Post-menopausal w/o prior adjuvant hormone therapy
Basic
Tamoxifen (, , , )
Tamoxifen (, , , )
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Limited
Tamoxifen
(Nonsteroidal AI if available)
Sequential hormone therapy** (, , , )
Tamoxifen
(Nonsteroidal AI if available)
Sequential hormone therapy** (, , , )
1048203
Enhanced
A nonsteroidal AI** and a CDK4/6 inhibitor (, , , )
A nonsteroidal AI** and a CDK4/6 inhibitor (, , , )
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1.1.5
Population
HR-positive, HER2-negative
Pre-menopausal
HR-positive, HER2-negative
Pre-menopausal
Basic
Tamoxifen
Bilateral oophorectomy (, , , )
Tamoxifen
Bilateral oophorectomy (, , , )
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Limited
Tamoxifen or alternate hormone therapy
Surgical options, e.g., bilateral oophorectomy; other options: OA/OS
Sequential hormone therapy if AI**
(, , , )
Tamoxifen or alternate hormone therapy
Surgical options, e.g., bilateral oophorectomy; other options: OA/OS
Sequential hormone therapy if AI**
(, , , )
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Enhanced
Ovarian suppression or ablation in combination with hormonal therapy (or if without exposure to prior hormone therapy, tamoxifen alone or ovarian suppression alone or ablation alone).
Sequential hormone therapy** (, , , )
Ovarian suppression or ablation in combination with hormonal therapy (or if without exposure to prior hormone therapy, tamoxifen alone or ovarian suppression alone or ablation alone).
Sequential hormone therapy** (, , , )
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1.1.6
Population
HR-positive, HER2-negative: postmenopausal
Pre-menopausal with treatment-naïve
HR-positive, HER2-negative: postmenopausal
Pre-menopausal with treatment-naïve
Basic
Tamoxifen (, , , )
Tamoxifen (, , , )
1048203
Limited
Tamoxifen or AI**
Nonsteroidal if available for postmenopausal
Tamoxifen with OA/OS if available for premenopausal or AI with OA/OS
If male patients, then with a gonadotropin-releasing hormone analog (, , , )
Tamoxifen or AI**
Nonsteroidal if available for postmenopausal
Tamoxifen with OA/OS if available for premenopausal or AI with OA/OS
If male patients, then with a gonadotropin-releasing hormone analog (, , , )
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Enhanced
Nonsteroidal AI** and a CDK4/6 inhibitor combined with ovarian function suppression (if male patients, then with a gonadotropin-releasing hormone analog) (, , , )
Nonsteroidal AI** and a CDK4/6 inhibitor combined with ovarian function suppression (if male patients, then with a gonadotropin-releasing hormone analog) (, , , )
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1.1.7
Population
HR-positive: recurrence within one year of completing adjuvant AI therapy
HR-positive: recurrence within one year of completing adjuvant AI therapy
Basic
Tamoxifen (, , , )
Tamoxifen (, , , )
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Limited
Alternative hormonal treatment (tamoxifen, steroidal aromatase inhibitor [SAI],** fulvestrant) (, , , )
Alternative hormonal treatment (tamoxifen, steroidal aromatase inhibitor [SAI],** fulvestrant) (, , , )
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Enhanced
Fulvestrant and a CDK4/6 inhibitor (, , , )
Fulvestrant and a CDK4/6 inhibitor (, , , )
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1.1.8
Population
HR-positive: recurrence ≥ 12 mos. of completing adjuvant therapy
HR-positive: recurrence ≥ 12 mos. of completing adjuvant therapy
Basic
Tamoxifen (, , , )
Tamoxifen (, , , )
1048203
Limited
May reuse specific hormone agent (, , , )
May reuse specific hormone agent (, , , )
1048203
Enhanced
AI** + CDK4/6 inhibitor
May reuse specific hormone agent (, , , )
AI** + CDK4/6 inhibitor
May reuse specific hormone agent (, , , )
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1.1.9
Population
Male breast cancer
Male breast cancer
Basic
Tamoxifen (, , , )
Tamoxifen (, , , )
1048203
Limited
Tamoxifen or (combined hormone blockage nonsteroidal aromatase inhibitor [NSAI] with luteinizing hormone-releasing hormone [LHRH] analog) (, , , )
Tamoxifen or (combined hormone blockage nonsteroidal aromatase inhibitor [NSAI] with luteinizing hormone-releasing hormone [LHRH] analog) (, , , )
1048203
Enhanced
Hormonal therapy (A nonsteroidal AI and a CDK4/6 inhibitor [with a gonadotropin-releasing hormone analog]) (, , , )
Hormonal therapy (A nonsteroidal AI and a CDK4/6 inhibitor [with a gonadotropin-releasing hormone analog]) (, , , )
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HER2-Positive
1.2.1
Population
HER2-positive (see below for additional options for HR-positive and HER2-positive)
HER2-positive (see below for additional options for HR-positive and HER2-positive)
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
Chemotherapy, options include anthracyclines (note: doxorubicin on EML), once weekly paclitaxel, docetaxel, carboplatin
Capecitabine (, , , )
Chemotherapy, options include anthracyclines (note: doxorubicin on EML), once weekly paclitaxel, docetaxel, carboplatin
Capecitabine (, , , )
1048203
Enhanced
HER2-targeted therapy combined with chemotherapy. Options include:trastuzumab, pertuzumab and a taxane
If pertuzumab not available, then chemotherapy and trastuzumab
If taxane not available, then vinorelbine or platinum (, , , )
HER2-targeted therapy combined with chemotherapy. Options include:trastuzumab, pertuzumab and a taxane
If pertuzumab not available, then chemotherapy and trastuzumab
If taxane not available, then vinorelbine or platinum (, , , )
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1.2.2
Population
HER2-positive, HR-positive
(In special circumstances such as low disease burden, the presence of co-morbidities [contradictions to HER2-targeted therapy such as congestive heart failure], and/or the presence of a long disease free-interval)
HER2-positive, HR-positive
(In special circumstances such as low disease burden, the presence of co-morbidities [contradictions to HER2-targeted therapy such as congestive heart failure], and/or the presence of a long disease free-interval)
Basic
Single-agent hormone therapy (tamoxifen).
Hormonal therapy with ovarian ablation. (, , , )
Single-agent hormone therapy (tamoxifen).
Hormonal therapy with ovarian ablation. (, , , )
1048203
Limited
Single-agent chemotherapy with anthracyclines, once weekly paclitaxel, docetaxel, carboplatin, cyclophosphamide, methotrexate, fluorouracil (CMF)
Hormonal therapy alone (if AI** and tamoxifen available) (, , , )
Single-agent chemotherapy with anthracyclines, once weekly paclitaxel, docetaxel, carboplatin, cyclophosphamide, methotrexate, fluorouracil (CMF)
Hormonal therapy alone (if AI** and tamoxifen available) (, , , )
1048203
Enhanced
HER2-targeted therapy (trastuzumab + pertuzumab) with chemotherapy or hormonal therapy plus HER2-targeted therapy or hormonal therapy alone (latter in special circumstances)
Clinicians should recommend HER2-targeted therapy-based combinations for first-line treatment, except for highly selected patients with estrogen receptor (ER) -positive or progesterone receptor (PgR) -positive and HER2-positive disease for whom clinicians may use endocrine therapy alone
In special circumstances, such as low disease burden, the presence of co-morbidities (contradictions to HER2-targeted therapy such as congestive heart failure), and/or the presence of a long disease free-interval, clinicians may offer first-line endocrine therapy alone (, , , )
HER2-targeted therapy (trastuzumab + pertuzumab) with chemotherapy or hormonal therapy plus HER2-targeted therapy or hormonal therapy alone (latter in special circumstances)
Clinicians should recommend HER2-targeted therapy-based combinations for first-line treatment, except for highly selected patients with estrogen receptor (ER) -positive or progesterone receptor (PgR) -positive and HER2-positive disease for whom clinicians may use endocrine therapy alone
In special circumstances, such as low disease burden, the presence of co-morbidities (contradictions to HER2-targeted therapy such as congestive heart failure), and/or the presence of a long disease free-interval, clinicians may offer first-line endocrine therapy alone (, , , )
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Triple-Negative
1.3.1
Population
Triple-negative without known PD-L1
Triple-negative without known PD-L1
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
Single-agent chemotherapy (, , , )
Single-agent chemotherapy (, , , )
1048203
Enhanced
Single-agent chemotherapy rather than combination chemotherapy (, , , )
Single-agent chemotherapy rather than combination chemotherapy (, , , )
1048203
1.3.2
Population
Triple-negative without known PD-L1 and with symptomatic or immediately life-threatening disease
Triple-negative without known PD-L1 and with symptomatic or immediately life-threatening disease
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
Single-agent chemotherapy
Combination chemotherapy if possible (, , , )
Single-agent chemotherapy
Combination chemotherapy if possible (, , , )
1048203
Enhanced
Single-agent chemotherapy
Combination chemotherapy if possible (, , , )
Single-agent chemotherapy
Combination chemotherapy if possible (, , , )
1048203
1.3.3
Population
Triple-negative with known PD-L1 and no contraindications
Triple-negative with known PD-L1 and no contraindications
Basic
Palliative* and best supportive care
(PD-L1 testing not available) (, , , )
Palliative* and best supportive care
(PD-L1 testing not available) (, , , )
1048203
Limited
Single-agent chemotherapy (, , , )
Single-agent chemotherapy (, , , )
1048203
Enhanced
Addition of immune checkpoint inhibitor to chemotherapy (atezolizumab plus nab-paclitaxel or pembrolizumab plus chemotherapy) as first-line therapy (, , , )
Addition of immune checkpoint inhibitor to chemotherapy (atezolizumab plus nab-paclitaxel or pembrolizumab plus chemotherapy) as first-line therapy (, , , )
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BRCA Mutations (note: the recommendations for patients with HR-positive, HER2-positive, and triple-negative breast cancer are also options for patients when PARPi are not available)
1.4.1.a
Population
BRCA1/2 mutations (HR-positive)
BRCA1/2 mutations (HR-positive)
Basic
Tamoxifen — If ER-positive, then see ER-positive recommendations and/or HER2-positive, see HER2-positive recommendations
Palliative* and best supportive care (, , , )
Tamoxifen — If ER-positive, then see ER-positive recommendations and/or HER2-positive, see HER2-positive recommendations
Palliative* and best supportive care (, , , )
1048203
Limited
Tamoxifen with OA
AI with OA
Single-agent chemotherapy rather than combination chemotherapy (, , , )
Tamoxifen with OA
AI with OA
Single-agent chemotherapy rather than combination chemotherapy (, , , )
1048203
Enhanced
PARPi
Single-agent chemotherapy rather than combination chemotherapy (, , , )
PARPi
Single-agent chemotherapy rather than combination chemotherapy (, , , )
1048203
1.4.1.b
Population
BRCA1/2 mutations, HR-negative, HER2-negative
BRCA1/2 mutations, HR-negative, HER2-negative
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
Single-agent chemotherapy (, , , )
Single-agent chemotherapy (, , , )
1048203
Enhanced
PARPiD/Chemotherapy (, , , )
PARPiD/Chemotherapy (, , , )
1048203
1.4.2
Population
HR-positive, HER2-negative, BRCA1/2 mutations (no longer benefiting from endocrine therapy)
HR-positive, HER2-negative, BRCA1/2 mutations (no longer benefiting from endocrine therapy)
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
Single-agent chemotherapy, combination regimens may be offered for symptomatic or immediately life-threatening disease especially carboplatin as first option (, , , )
Single-agent chemotherapy, combination regimens may be offered for symptomatic or immediately life-threatening disease especially carboplatin as first option (, , , )
1048203
Enhanced
PARPi (in the first- through to third-line setting rather than chemotherapy), if not available, then single-agent chemotherapy, combination regimens may be offered for symptomatic or immediately life-threatening disease (, , , )
PARPi (in the first- through to third-line setting rather than chemotherapy), if not available, then single-agent chemotherapy, combination regimens may be offered for symptomatic or immediately life-threatening disease (, , , )
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Overview
Title
Systemic Treatment of Patients with Metastatic Breast Cancer
Authoring Organization
American Society of Clinical Oncology