Systemic Treatment of Patients with Metastatic Breast Cancer
Publication Date: January 9, 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 (, , , )
1048203
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 (, , , )
1048203
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 (, , , )
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 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 (, , , )
1048203
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 (, , , )
1048203
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 (, , , )
1048203
1.1.5
Population
HR-positive, HER2-negative
Pre-menopausal
HR-positive, HER2-negative
Pre-menopausal
Basic
Tamoxifen
Bilateral oophorectomy (, , , )
Tamoxifen
Bilateral oophorectomy (, , , )
1048203
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**
(, , , )
1048203
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** (, , , )
1048203
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 (, , , )
1048203
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) (, , , )
1048203
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 (, , , )
1048203
Limited
Alternative hormonal treatment (tamoxifen, steroidal aromatase inhibitor [SAI],** fulvestrant) (, , , )
Alternative hormonal treatment (tamoxifen, steroidal aromatase inhibitor [SAI],** fulvestrant) (, , , )
1048203
Enhanced
Fulvestrant and a CDK4/6 inhibitor (, , , )
Fulvestrant and a CDK4/6 inhibitor (, , , )
1048203
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 (, , , )
1048203
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]) (, , , )
1048203
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 (, , , )
1048203
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 (, , , )
1048203
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 (, , , )
1048203
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 (, , , )
1048203
Table 4. Second-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 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.
* Palliative care may or may not include radiation therapy for symptom control.
Italics = medications on 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.
* Palliative care may or may not include radiation therapy for symptom control.
HR-Positive, HER2-Negative
2.1.1
Population
HR-positive, HER2-negative, no longer benefiting from endocrine therapy
HR-positive, HER2-negative, 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 (, , , )
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 (, , , )
1048203
2.1.2
Population
HR-positive, HER2-negative
Post-menopausal MBC progressing on prior treatment with nonsteroidal AIs, either before or after treatment with fulvestrant
HR-positive, HER2-negative
Post-menopausal MBC progressing on prior treatment with nonsteroidal AIs, either before or after treatment with fulvestrant
Basic
Tamoxifen if previously not used (, , , )
Tamoxifen if previously not used (, , , )
1048203
Limited
Tamoxifen or single-agent chemotherapy, combination regimens may be offered for symptomatic or immediately life-threatening disease (, , , )
Tamoxifen or single-agent chemotherapy, combination regimens may be offered for symptomatic or immediately life-threatening disease (, , , )
1048203
Enhanced
Exemestane and everolimus (, , , )
Exemestane and everolimus (, , , )
1048203
2.1.3
Population
Postmenopausal women, and male patients, with HR-positive, HER2-negative, PIK3CA mutation, advanced breast cancer (ABC), or MBC following prior endocrine therapy including an AI, with or without a CDK4/6 inhibitor
Postmenopausal women, and male patients, with HR-positive, HER2-negative, PIK3CA mutation, advanced breast cancer (ABC), or MBC following prior endocrine therapy including an AI, with or without a CDK4/6 inhibitor
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
Tamoxifen or single-agent* chemotherapy, combination regimens may be offered for symptomatic or immediately life-threatening disease
(Careful screening for and management of common toxicities are required) (, , , )
Tamoxifen or single-agent* chemotherapy, combination regimens may be offered for symptomatic or immediately life-threatening disease
(Careful screening for and management of common toxicities are required) (, , , )
1048203
Enhanced
Alpelisib in combination with endocrine therapy in combination with fulvestrant
(Careful screening for and management of common toxicities are required) (, , , )
Alpelisib in combination with endocrine therapy in combination with fulvestrant
(Careful screening for and management of common toxicities are required) (, , , )
1048203
2.1.4
Population
Postmenopausal women, with HR-positive, HER2-negative, without PIK3CA mutation, MBC following prior endocrine therapy including an AI, with or without a CDK4/6 inhibitor
Postmenopausal women, with HR-positive, HER2-negative, without PIK3CA mutation, MBC following prior endocrine therapy including an AI, with or without a CDK4/6 inhibitor
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
Tamoxifen or single-agent chemotherapy, combination regimens may be offered for symptomatic or immediately life-threatening disease (, , , )
Tamoxifen or single-agent chemotherapy, combination regimens may be offered for symptomatic or immediately life-threatening disease (, , , )
1048203
Enhanced
Endocrine therapy, AI, or fulvestrant ± everolimus (, , , )
Endocrine therapy, AI, or fulvestrant ± everolimus (, , , )
1048203
2.1.5
Population
HR-positive, HER2-negative with recurrence on prior hormone therapy with or without targeted therapy with immediately life-threatening disease or in those with rapid visceral recurrence on adjuvant endocrine therapy
HR-positive, HER2-negative with recurrence on prior hormone therapy with or without targeted therapy with immediately life-threatening disease or in those with rapid visceral recurrence on adjuvant endocrine therapy
Basic
Hormone therapy
Palliative* care and best supportive care (, , , )
Hormone therapy
Palliative* care 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
Hormone therapy with or without targeted therapy or single-agent chemotherapy (, , , )
Hormone therapy with or without targeted therapy or single-agent chemotherapy (, , , )
1048203
2.1.6
Population
HR-positive, HER2-negative, with germline BRCA1/2 mutation no longer benefiting from hormone therapy
HR-positive, HER2-negative, with germline BRCA1/2 mutation no longer benefiting from hormone 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
Single-agent chemotherapy, combination regimens may be offered for symptomatic or immediately life-threatening disease especially carboplatin as first option (, , , )
PARPi
Single-agent chemotherapy, combination regimens may be offered for symptomatic or immediately life-threatening disease especially carboplatin as first option (, , , )
1048203
HER2-Positive
2.2.1
Population
HER2-positive
HER2-positive
Basic
Palliative* and best supportive care
(HER2 testing likely not available) (, , , )
Palliative* and best supportive care
(HER2 testing likely not available) (, , , )
1048203
Limited
Chemotherapy (anthracyclines, docetaxel, once weekly paclitaxel, carboplatin, CMF)
Capecitabine
Capecitabine + lapatinib
Trastuzumab with second-line chemotherapy (, , , )
Chemotherapy (anthracyclines, docetaxel, once weekly paclitaxel, carboplatin, CMF)
Capecitabine
Capecitabine + lapatinib
Trastuzumab with second-line chemotherapy (, , , )
1048203
Enhanced
(1) Trastuzumab deruxtecan.
If 1 not available, then 2:
(2) Trastuzumab emtansine
Other options, if 2 not available then 3:
(3) Capecitabine + lapatinib
If 3 not available then 4:
(4) Trastuzumab with second-line chemotherapy (, , , )
(1) Trastuzumab deruxtecan.
If 1 not available, then 2:
(2) Trastuzumab emtansine
Other options, if 2 not available then 3:
(3) Capecitabine + lapatinib
If 3 not available then 4:
(4) Trastuzumab with second-line chemotherapy (, , , )
1048203
2.2.2
Population
HER2-positive, received HER2-targeted therapy and chemotherapy in first-line
HER2-positive, received HER2-targeted therapy and chemotherapy in first-line
Basic
(Total mastectomy for ipsilateral in-breast recurrence if single bone metastasis only). If no medical treatment available, and no pathology, for palliative reasons, including local control, primary surgery in patients who are symptomatic when systemic anti-HER2 therapy is not available (, , , )
(Total mastectomy for ipsilateral in-breast recurrence if single bone metastasis only). If no medical treatment available, and no pathology, for palliative reasons, including local control, primary surgery in patients who are symptomatic when systemic anti-HER2 therapy is not available (, , , )
1048203
Limited
Chemotherapy with anthracyclines, docetaxel, once weekly paclitaxel, and carboplatin, CMF
Capecitabine
Hormonal therapy alone (, , , )
Chemotherapy with anthracyclines, docetaxel, once weekly paclitaxel, and carboplatin, CMF
Capecitabine
Hormonal therapy alone (, , , )
1048203
Enhnaced
(1) Trastuzumab deruxtecan.
If 1 not available, then 2:
(2) Trastuzumab emtansine
Other options, if 2 not available then 3:
(3) Capecitabine + lapatinib
If 3 not available then 4:
(4) Trastuzumab with second-line chemotherapy (, , , )
(1) Trastuzumab deruxtecan.
If 1 not available, then 2:
(2) Trastuzumab emtansine
Other options, if 2 not available then 3:
(3) Capecitabine + lapatinib
If 3 not available then 4:
(4) Trastuzumab with second-line chemotherapy (, , , )
1048203
2.2.3
Population
HER2-positive
If a patient finished trastuzumab-based adjuvant treatment ≤12 months before recurrence
HER2-positive
If a patient finished trastuzumab-based adjuvant treatment ≤12 months before recurrence
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
Chemotherapy (anthracyclines, docetaxel, carboplatin, CMF, capecitabine) (, , , )
Chemotherapy (anthracyclines, docetaxel, carboplatin, CMF, capecitabine) (, , , )
1048203
Enhanced
(1) Trastuzumab deruxtecan.
If 1 not available, then 2:
(2) Trastuzumab emtansine
Other options, if 2 not available then 3:
(3) Capecitabine + lapatinib
If 3 not available then 4:
(4) Trastuzumab with second-line chemotherapy
(, , , )
(1) Trastuzumab deruxtecan.
If 1 not available, then 2:
(2) Trastuzumab emtansine
Other options, if 2 not available then 3:
(3) Capecitabine + lapatinib
If 3 not available then 4:
(4) Trastuzumab with second-line chemotherapy
(, , , )
1048203
2.2.4
Population
HER2-positive
If a patient finished trastuzumab-based adjuvant treatment >12 months before recurrence
HER2-positive
If a patient finished trastuzumab-based adjuvant treatment >12 months before recurrence
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
Chemotherapy (anthracyclines, once weekly paclitaxel, docetaxel, carboplatin) (, , , )
Chemotherapy (anthracyclines, once weekly paclitaxel, docetaxel, carboplatin) (, , , )
1048203
Enhanced
HER2-targeted therapy combined with chemotherapy
Trastuzumab, pertuzumab and a taxane.
If pertuzumab not available, then chemotherapy and trastuzumab. If taxane not available, then vinorelbine, platinum (, , , )
HER2-targeted therapy combined with chemotherapy
Trastuzumab, pertuzumab and a taxane.
If pertuzumab not available, then chemotherapy and trastuzumab. If taxane not available, then vinorelbine, platinum (, , , )
1048203
Triple-Negative
2.3.1
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 (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
Single-agent chemotherapy; start with sequencing taxane or platinum; may offer metronomic chemotherapy for disease control (, , , )
Single-agent chemotherapy; start with sequencing taxane or platinum; may offer metronomic chemotherapy for disease control (, , , )
1048203
Enhanced
Single-agent chemotherapy rather than combination chemotherapy
Start with sequencing taxane or platinum; may offer metronomic chemotherapy for disease control (, , , )
Single-agent chemotherapy rather than combination chemotherapy
Start with sequencing taxane or platinum; may offer metronomic chemotherapy for disease control (, , , )
1048203
Table 5. Maximal Setting: Third-line Options for HER2-Positive Breast Cancer
Italics, Underlined = not on EML
Italics = medications on EML (not universally available in low-income and lower-middle-income countries [<50%])
Italics = medications on EML (not universally available in low-income and lower-middle-income countries [<50%])
If a patient’s HER2-positive advanced breast cancer has progressed during or after second line or greater HER2-targeted treatment and the patient has already received pertuzumab and trastuzumab deruxtecan (TDxd), (if a patient has not received pertuzumab, pertuzumab) (, , , )
1048203
If a patient has not received trastuzumab emtansine (T-DM1) in second-line, T-DM1 regimen (, , , S)
1048203
Tucatinib combined with trastuzumab and capecitabine (, , , S)
1048203
Trastuzumab deruxtecan (, , , S)
1048203
Neratinib combined with capecitabine (, , , W)
1048203
Lapatinib and trastuzumab (, , , W)
1048203
Lapatinib and capecitabine (, , , W)
1048203
Other combinations of chemotherapy and trastuzumab (, , , W)
1048203
Margetuximab plus chemotherapy (, , , W)
1048203
If a patient has not received pertuzumab, pertuzumab (, , , W)
1048203
Hormonal therapy (in patients with ER-positive and/or PgR-positive disease) (, , , W)
1048203
Abemaciclib combined with trastuzumab and fulvestrant (, , , W)
1048203
Table 6. Third-Line and Beyond 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 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.
* Palliative care may or may not include radiation therapy for symptom control.
Italics = medications on 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.
* Palliative care may or may not include radiation therapy for symptom control.
Triple-Negative
3.1.1
Population
Triple-negative
Triple-negative
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Enhanced
Single-agent chemotherapy rather than combination chemotherapy. (, , , )
Single-agent chemotherapy rather than combination chemotherapy. (, , , )
1048203
3.1.2
Population
Triple-negative with germline BRCA1/2 mutations (previously been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting)
Triple-negative with germline BRCA1/2 mutations (previously been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting)
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
PARPi (for those with known mutation status) (, , , )
PARPi (for those with known mutation status) (, , , )
1048203
Enhanced
PARPi (for those with known mutation status) (, , , )
PARPi (for those with known mutation status) (, , , )
1048203
HR-positive, BRCA mutation
3.2.1
Population
HR-positive, germline BRCA1/2 mutation
HR-positive, germline BRCA1/2 mutation
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
PARPi (for those with known mutation status) (, , , )
PARPi (for those with known mutation status) (, , , )
1048203
Enhanced
PARPi (for those with known mutation status)
Single-agent chemotherapy rather than combination chemotherapy (, , , )
PARPi (for those with known mutation status)
Single-agent chemotherapy rather than combination chemotherapy (, , , )
1048203
HER2-Positive
3.3.1
Population
HER2-positive
HER2-positive
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
Chemotherapy (, , , )
Chemotherapy (, , , )
1048203
Enhanced
Trastuzumab emtansine (, , , )
Trastuzumab emtansine (, , , )
1048203
3.3.2
Population
HER2-positive, HR-positive
HER2-positive, HR-positive
Basic
Palliative* and best supportive care (, , , )
Palliative* and best supportive care (, , , )
1048203
Limited
Hormonal therapy (, , , )
Hormonal therapy (, , , )
1048203
Enhanced
Trastuzumab + hormonal therapy (, , , )
Trastuzumab + hormonal therapy (, , , )
1048203
3.3.3
Population
Patient is receiving HER2-targeted therapy and chemotherapy combinations
(Timing, Duration, Scheduling — ASCO question — what are the optimal timing, dose, schedule, and duration of treatment)
Patient is receiving HER2-targeted therapy and chemotherapy combinations
(Timing, Duration, Scheduling — ASCO question — what are the optimal timing, dose, schedule, and duration of treatment)
Basic
Not relevant (, , , )
Not relevant (, , , )
1048203
Limited
If a patient is receiving HER2-targeted therapy and chemotherapy combinations, the chemotherapy should continue for approximately 4–6 months (or longer) and/or to the time of maximal response, depending on toxicity and in the absence of progression. When chemotherapy is stopped, clinicians should continue the HER2-targeted therapy; no further change in the regimen is needed until the time of progression or unacceptable toxicities. (, , , )
If a patient is receiving HER2-targeted therapy and chemotherapy combinations, the chemotherapy should continue for approximately 4–6 months (or longer) and/or to the time of maximal response, depending on toxicity and in the absence of progression. When chemotherapy is stopped, clinicians should continue the HER2-targeted therapy; no further change in the regimen is needed until the time of progression or unacceptable toxicities. (, , , )
1048203
Enhanced
If a patient is receiving HER2-targeted therapy and chemotherapy combinations, the chemotherapy should continue for approximately 4–6 months (or longer) and/or to the time of maximal response, depending on toxicity and in the absence of progression. When chemotherapy is stopped, clinicians should continue the HER2-targeted therapy; no further change in the regimen is needed until the time of progression or unacceptable toxicities. (, , , )
If a patient is receiving HER2-targeted therapy and chemotherapy combinations, the chemotherapy should continue for approximately 4–6 months (or longer) and/or to the time of maximal response, depending on toxicity and in the absence of progression. When chemotherapy is stopped, clinicians should continue the HER2-targeted therapy; no further change in the regimen is needed until the time of progression or unacceptable toxicities. (, , , )
1048203
Recommendation Grading
Disclaimer
The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.
Overview
Title
Systemic Treatment of Patients with Metastatic Breast Cancer
Authoring Organization
American Society of Clinical Oncology
Publication Month/Year
January 9, 2024
Last Updated Month/Year
February 6, 2024
Supplemental Implementation Tools
Document Type
Guideline
Country of Publication
US
Document Objectives
To provide expert guidance on the systemic treatment of metastatic breast cancer to clinicians, public health leaders, patients, and policymakers in resource-constrained settings.
Target Patient Population
Adult patients with metastatic breast cancer in resource-constrained settings and focuses on medical treatment
Inclusion Criteria
Male, Female, Adult, Older adult
Health Care Settings
Ambulatory, Outpatient
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Treatment
Diseases/Conditions (MeSH)
D018567 - Breast Neoplasms, Male, D001943 - Breast Neoplasms, D009362 - Neoplasm Metastasis
Keywords
breast cancer, tamoxifen, exemestane, trastuzumab, chemotherapy, capecitabine, pertuzumab, paclitaxel, docetaxel, carboplatin, fulvestrant, everolimus, hormonal therapy, systemic therapy, BRCA, HER2 Positive, BRCA1, BRCA2, PIK3CA, BRCA 1/2 testing, HR-Positive, Triple-Negative Breast Cancer, resource-constrained settings, PARPi, alpelisib, anthracyclines, CMF, lapatinib, taxane, Trastuzumab emtansine, Trastuzumab deruxtecan
Source Citation
Al Sukhun S, Temin S, Barrios CH, et al. Systemic Treatment of Patients with Metastatic Breast Cancer: ASCO Resource-Stratified Guideline. JCO Glob Oncol. 2023 Jan 10. doi:10.1200/GO.23.00285.