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Breast Cancer Locally Advanced and Inflammatory Breast Cancer e Inflammatory breast cancer, characterized by swelling, thickening, and erythema of the skin overlying the Locally advanced breast cancer includes a subset of clinical breast, may be mistaken for infectious mastitis and stage IIB cancers (T3NOMO), as well as stages IIIA to IIIC can- delay evaluation and treatment. cers. These cancers may have high-risk characteristics such as skin involvement, chest wall involvement, extensive lymph e Locally advanced cancers are usually treated with neo- node involvement, or inflammatory changes. adjuvant chemotherapy or endocrine therapy, surgery, Inflammatory breast cancer represents a small subset of and irradiation.

Locally Advanced and Inflammatory Breast Cancer e Inflammatory breast cancer, characterized by swelling, thickening, and erythema of the skin overlying the Locally advanced breast cancer includes a subset of clinical breast, may be mistaken for infectious mastitis and stage IIB cancers (T3NOMO), as well as stages IIIA to IIIC can- delay evaluation and treatment. cers. These cancers may have high-risk characteristics such as skin involvement, chest wall involvement, extensive lymph e Locally advanced cancers are usually treated with neo- node involvement, or inflammatory changes. adjuvant chemotherapy or endocrine therapy, surgery, Inflammatory breast cancer represents a small subset of and irradiation. locally advanced breast cancer in which patients present with swelling, thickening, or erythema of the skin overlying the Breast Cancer Follow-up breast, classically with a peau d’orange (orange peel) appear- ance (Figure 2). Patients often present with breast enlarge- and Survivorship ment or swelling, often misdiagnosed as mastitis with There are nearly 3 million women alive in the United States subsequent delay in management. A palpable breast mass may with a previous or current diagnosis of breast cancer. Following be present. The skin changes are due to the obstruction of early active therapy (surgery, chemotherapy, and irradiation), dermal lymphatic vessels by cancer cells, although biopsy may patients are monitored for recurrence, second primary can- not always reveal that pathology. One third of patients have cers, and physical and psychosocial long-term effects ofbreast distant metastases at diagnosis, and nearly all have lymph cancer and treatment. Patients with hormone receptor- node involvement. For this reason, these patients should have positive breast cancer remain on antiestrogen treatment for 5 routine staging with either CT and bone scan imaging or PET to 10 years and require management of menopausal symptoms scan, even in the absence of metastatic disease symptoms. and other toxicities, including bone loss, during that time. Locally advanced cancers are usually treated initially with Guidelines recommend that patients be evaluated for a detailed neoadjuvant chemotherapy, followed by surgery, and then irra- cancer-related history and physical examination every 3 to diation. In some postmenopausal women, neoadjuvant anties- 6 months for the first 3 years, every 6 to 12 months for the next trogen therapy can be used instead of chemotherapy. Patients 2 years, and then annually. with inflammatory breast cancer require mastectomy, but in Patients should have annual mammograms of remain- other patients, neoadjuvant therapy may decrease the size of ing breast tissue. Screening breast MRIs are needed only the primary breast cancer to allow for breast-conserving if patients meet criteria for screening MRIs (see lumpectomy. Patients will generally receive radiation therapy Chemoprevention and other Risk Reduction Strategies). afterward. The amount of residual cancer after neoadjuvant Patients should not have routine blood tests at follow-up chemotherapy has prognostic significance, particularly in visits or other routine imaging studies, as these are not help- triple-negative or hormone-negative, HER2-positive cancers. ful for diagnosing recurrences earlier. Laboratory and imag- Patients with complete pathologic responses have the lowest ing studies other than breast imaging should be guided by a

locally advanced breast cancer in which patients present with swelling, thickening, or erythema of the skin overlying the Breast Cancer Follow-up breast, classically with a peau d’orange (orange peel) appear- ance (Figure 2). Patients often present with breast enlarge- and Survivorship ment or swelling, often misdiagnosed as mastitis with There are nearly 3 million women alive in the United States subsequent delay in management. A palpable breast mass may with a previous or current diagnosis of breast cancer. Following be present. The skin changes are due to the obstruction of early active therapy (surgery, chemotherapy, and irradiation), dermal lymphatic vessels by cancer cells, although biopsy may patients are monitored for recurrence, second primary can- not always reveal that pathology. One third of patients have cers, and physical and psychosocial long-term effects ofbreast distant metastases at diagnosis, and nearly all have lymph cancer and treatment. Patients with hormone receptor- node involvement. For this reason, these patients should have positive breast cancer remain on antiestrogen treatment for 5 routine staging with either CT and bone scan imaging or PET to 10 years and require management of menopausal symptoms scan, even in the absence of metastatic disease symptoms. and other toxicities, including bone loss, during that time. Locally advanced cancers are usually treated initially with Guidelines recommend that patients be evaluated for a detailed neoadjuvant chemotherapy, followed by surgery, and then irra- cancer-related history and physical examination every 3 to diation. In some postmenopausal women, neoadjuvant anties- 6 months for the first 3 years, every 6 to 12 months for the next trogen therapy can be used instead of chemotherapy. Patients 2 years, and then annually. with inflammatory breast cancer require mastectomy, but in Patients should have annual mammograms of remain- other patients, neoadjuvant therapy may decrease the size of ing breast tissue. Screening breast MRIs are needed only the primary breast cancer to allow for breast-conserving if patients meet criteria for screening MRIs (see lumpectomy. Patients will generally receive radiation therapy Chemoprevention and other Risk Reduction Strategies). afterward. The amount of residual cancer after neoadjuvant Patients should not have routine blood tests at follow-up chemotherapy has prognostic significance, particularly in visits or other routine imaging studies, as these are not help- triple-negative or hormone-negative, HER2-positive cancers. ful for diagnosing recurrences earlier. Laboratory and imag- Patients with complete pathologic responses have the lowest ing studies other than breast imaging should be guided by a risk of recurrence, whereas those with residual disease may patient’s symptoms or findings on examination that raise benefit from treatment intensification with additional concern for recurrence.

locally advanced breast cancer in which patients present with swelling, thickening, or erythema of the skin overlying the Breast Cancer Follow-up breast, classically with a peau d’orange (orange peel) appear- ance (Figure 2). Patients often present with breast enlarge- and Survivorship ment or swelling, often misdiagnosed as mastitis with There are nearly 3 million women alive in the United States subsequent delay in management. A palpable breast mass may with a previous or current diagnosis of breast cancer. Following be present. The skin changes are due to the obstruction of early active therapy (surgery, chemotherapy, and irradiation), dermal lymphatic vessels by cancer cells, although biopsy may patients are monitored for recurrence, second primary can- not always reveal that pathology. One third of patients have cers, and physical and psychosocial long-term effects ofbreast distant metastases at diagnosis, and nearly all have lymph cancer and treatment. Patients with hormone receptor- node involvement. For this reason, these patients should have positive breast cancer remain on antiestrogen treatment for 5 routine staging with either CT and bone scan imaging or PET to 10 years and require management of menopausal symptoms scan, even in the absence of metastatic disease symptoms. and other toxicities, including bone loss, during that time. Locally advanced cancers are usually treated initially with Guidelines recommend that patients be evaluated for a detailed neoadjuvant chemotherapy, followed by surgery, and then irra- cancer-related history and physical examination every 3 to diation. In some postmenopausal women, neoadjuvant anties- 6 months for the first 3 years, every 6 to 12 months for the next trogen therapy can be used instead of chemotherapy. Patients 2 years, and then annually. with inflammatory breast cancer require mastectomy, but in Patients should have annual mammograms of remain- other patients, neoadjuvant therapy may decrease the size of ing breast tissue. Screening breast MRIs are needed only the primary breast cancer to allow for breast-conserving if patients meet criteria for screening MRIs (see lumpectomy. Patients will generally receive radiation therapy Chemoprevention and other Risk Reduction Strategies). afterward. The amount of residual cancer after neoadjuvant Patients should not have routine blood tests at follow-up chemotherapy has prognostic significance, particularly in visits or other routine imaging studies, as these are not help- triple-negative or hormone-negative, HER2-positive cancers. ful for diagnosing recurrences earlier. Laboratory and imag- Patients with complete pathologic responses have the lowest ing studies other than breast imaging should be guided by a risk of recurrence, whereas those with residual disease may patient’s symptoms or findings on examination that raise benefit from treatment intensification with additional concern for recurrence. chemotherapy. Patients should be evaluated at each visit for changes in family history of cancers and referred for genetic counseling as appropriate. Patients on tamoxifen should have annual gynecologic examinations and be evaluated by a gynecologist for any abnormal vaginal bleeding. Patients on aromatase inhibitors should have bone density studies every 2 years and should receive osteoporosis treatment, ideally with a bisphos- phonate, if their T score is -2.5 or lower. For patients with breast asymmetry, reconstruction options are often fully covered by insurance. Patients should receive physical therapy for lymphedema or decreased arm mobility after surgery or irradiation to axillary nodes. Menopausal symp- toms should be managed with nonhormonal options, such as gabapentin for nocturnal hot flushes. Depression, anxiety, and sexual dysfunction are not uncommon in this population and should be appropriately assessed and managed. For patients taking tamoxifen, it is important to avoid medications with FIGURE 2. Inflammatory breast cancer often has a characteristic “p'eau d'orange" (orange peel) appearance of the skin, due to tumor emboli in the dermal lymphatics. strong CYP2D6 inhibition, such as bupropion or fluoxetine, as Erythema is also often present. these may decrease tamoxifen activation.

chemotherapy. Patients should be evaluated at each visit for changes in family history of cancers and referred for genetic counseling as appropriate. Patients on tamoxifen should have annual gynecologic examinations and be evaluated by a gynecologist for any abnormal vaginal bleeding. Patients on aromatase inhibitors should have bone density studies every 2 years and should receive osteoporosis treatment, ideally with a bisphos- phonate, if their T score is -2.5 or lower. For patients with breast asymmetry, reconstruction options are often fully covered by insurance. Patients should receive physical therapy for lymphedema or decreased arm mobility after surgery or irradiation to axillary nodes. Menopausal symp- toms should be managed with nonhormonal options, such as gabapentin for nocturnal hot flushes. Depression, anxiety, and sexual dysfunction are not uncommon in this population and should be appropriately assessed and managed. For patients taking tamoxifen, it is important to avoid medications with FIGURE 2. Inflammatory breast cancer often has a characteristic “p'eau d'orange" (orange peel) appearance of the skin, due to tumor emboli in the dermal lymphatics. strong CYP2D6 inhibition, such as bupropion or fluoxetine, as Erythema is also often present. these may decrease tamoxifen activation. 12

Breast Cancer aromatase inhibitor improves the response rate and duration of response to hormonal therapy. These drugs have been incor- e After completing treatment for breast cancer, follow-up porated into routine care for the majority of women with monitoring should be every 3 to 6 months for the first metastatic estrogen receptor-positive/ HER2-negative breast 3 years, every 6 to 12 months for the next 2 years, and cancer. then every year, with annual mammography for all survi- For patients with HER2-positive advanced breast cancer, vors, and breast MRI for those at high risk of recurrence. treatment should include HER2-directed therapy such as tras- HVC e Surveillance blood tests and other imaging tests for tuzumab given with either chemotherapy or antiestrogen breast cancer should not be routinely performed and therapy, depending on the hormone receptor status of the should be guided by a patient’s symptoms or findings cancer and disease sites. First-line treatment with dual HER2- on examination that raise concern for recurrence. targeted therapy with trastuzumab and pertuzumab added to e Patients taking tamoxifen should have yearly gyneco- the taxane docetaxel has been shown to improve overall sur- logic examinations because of the increased risk of vival, with median overall survival of 56 months in a phase III endometrial cancer, and those on an aromatase inhibi- clinical trial. Ado-trastuzumab emtansine is commonly used tor should have bone density studies every other year to as a second-line treatment but may be used as first-line ther- assess osteoporosis. apy following a treatment-free interval of less than 6 months from adjuvant trastuzumab. Patients with triple-negative breast cancers (TNBC have a Metastatic Breast Cancer higher relapse rate than individuals with hormone receptor- Approximately 5% of patients with breast cancer present with positive cancers; recur earlier, with a peak at 3 years after diag- metastatic disease, and up to 30% with early-stage disease nosis and a very low risk of relapse after 5 years; and have a develop metastases. Metastatic breast cancer is not curable, but higher risk of locoregional recurrence and brain and lung systemic therapy can improve survival, relieve symptoms, and metastases. Advanced TNBC has historically been treated with maintain quality of life. Treatment and prognosis are related to chemotherapy. The addition of atezolizumab, a monoclonal whether visceral metastases are present, the number of sites antibody targeting programmed death ligand 1, to nab- involved, the interval between initial diagnosis and metastases paclitaxel improved overall survival (23.1 vs 17.6 months) for (intervals of less than 2 years have a poorer prognosis), the patients with programmed death ligand 1-positive metastatic patient’s performance status, and tumor biology. The median TNBC. TNBC may also be particularly responsive to platinum overall survival for patients with metastatic breast cancer is agents, particularly in BRCA mutation carriers. In patients with longer for women with hormone receptor-positive cancer or germline BRCA1 or BRCA2 mutations, poly (ADP-ribose) poly- HER2-positive cancer, some of whom may have prolonged merase inhibitors (olaparib, talazoparib) improve progression- survival, in part related to more treatment options. free survival relative to single-agent chemotherapy. These When evaluating a patient with newly diagnosed meta- agents cause “synthetic lethality” by producing an increase in static breast cancer, the lesion that upstages the patient to the double-strand DNA breaks that would usually be repaired by greatest degree should be biopsied. It is also important to the BRCA pathway. biopsy a site of initial metastasis both to confirm the diagnosis Chemotherapy agents used in patients with advanced and to assess hormone receptor and HER2 status, as there may breast cancer include taxanes, capecitabine, eribulin, gemcit- be treatment altering discordance in the receptors in the meta- abine, vinorelbine, ixabepilone, and liposomal doxorubicin. static lesion compared with the primary breast cancer in 10% Single-agent chemotherapy is usually given, with combination to 15% of patients. chemotherapy reserved for patients with extensive visceral In postmenopausal women with hormone receptor-pos- itive, HER2-negative breast cancer, endocrine-based therapy metastases where a higher response rate is important.

aromatase inhibitor improves the response rate and duration of response to hormonal therapy. These drugs have been incor- e After completing treatment for breast cancer, follow-up porated into routine care for the majority of women with monitoring should be every 3 to 6 months for the first metastatic estrogen receptor-positive/ HER2-negative breast 3 years, every 6 to 12 months for the next 2 years, and cancer. then every year, with annual mammography for all survi- For patients with HER2-positive advanced breast cancer, vors, and breast MRI for those at high risk of recurrence. treatment should include HER2-directed therapy such as tras- HVC e Surveillance blood tests and other imaging tests for tuzumab given with either chemotherapy or antiestrogen breast cancer should not be routinely performed and therapy, depending on the hormone receptor status of the should be guided by a patient’s symptoms or findings cancer and disease sites. First-line treatment with dual HER2- on examination that raise concern for recurrence. targeted therapy with trastuzumab and pertuzumab added to e Patients taking tamoxifen should have yearly gyneco- the taxane docetaxel has been shown to improve overall sur- logic examinations because of the increased risk of vival, with median overall survival of 56 months in a phase III endometrial cancer, and those on an aromatase inhibi- clinical trial. Ado-trastuzumab emtansine is commonly used tor should have bone density studies every other year to as a second-line treatment but may be used as first-line ther- assess osteoporosis. apy following a treatment-free interval of less than 6 months from adjuvant trastuzumab. Patients with triple-negative breast cancers (TNBC have a Metastatic Breast Cancer higher relapse rate than individuals with hormone receptor- Approximately 5% of patients with breast cancer present with positive cancers; recur earlier, with a peak at 3 years after diag- metastatic disease, and up to 30% with early-stage disease nosis and a very low risk of relapse after 5 years; and have a develop metastases. Metastatic breast cancer is not curable, but higher risk of locoregional recurrence and brain and lung systemic therapy can improve survival, relieve symptoms, and metastases. Advanced TNBC has historically been treated with maintain quality of life. Treatment and prognosis are related to chemotherapy. The addition of atezolizumab, a monoclonal whether visceral metastases are present, the number of sites antibody targeting programmed death ligand 1, to nab- involved, the interval between initial diagnosis and metastases paclitaxel improved overall survival (23.1 vs 17.6 months) for (intervals of less than 2 years have a poorer prognosis), the patients with programmed death ligand 1-positive metastatic patient’s performance status, and tumor biology. The median TNBC. TNBC may also be particularly responsive to platinum overall survival for patients with metastatic breast cancer is agents, particularly in BRCA mutation carriers. In patients with longer for women with hormone receptor-positive cancer or germline BRCA1 or BRCA2 mutations, poly (ADP-ribose) poly- HER2-positive cancer, some of whom may have prolonged merase inhibitors (olaparib, talazoparib) improve progression- survival, in part related to more treatment options. free survival relative to single-agent chemotherapy. These When evaluating a patient with newly diagnosed meta- agents cause “synthetic lethality” by producing an increase in static breast cancer, the lesion that upstages the patient to the double-strand DNA breaks that would usually be repaired by greatest degree should be biopsied. It is also important to the BRCA pathway. biopsy a site of initial metastasis both to confirm the diagnosis Chemotherapy agents used in patients with advanced and to assess hormone receptor and HER2 status, as there may breast cancer include taxanes, capecitabine, eribulin, gemcit- be treatment altering discordance in the receptors in the meta- abine, vinorelbine, ixabepilone, and liposomal doxorubicin. static lesion compared with the primary breast cancer in 10% Single-agent chemotherapy is usually given, with combination to 15% of patients. chemotherapy reserved for patients with extensive visceral In postmenopausal women with hormone receptor-pos- itive, HER2-negative breast cancer, endocrine-based therapy metastases where a higher response rate is important. is usually the initial treatment. In patients with rapidly pro- For all subtypes of breast cancer with bone metastases,

aromatase inhibitor improves the response rate and duration of response to hormonal therapy. These drugs have been incor- e After completing treatment for breast cancer, follow-up porated into routine care for the majority of women with monitoring should be every 3 to 6 months for the first metastatic estrogen receptor-positive/ HER2-negative breast 3 years, every 6 to 12 months for the next 2 years, and cancer. then every year, with annual mammography for all survi- For patients with HER2-positive advanced breast cancer, vors, and breast MRI for those at high risk of recurrence. treatment should include HER2-directed therapy such as tras- HVC e Surveillance blood tests and other imaging tests for tuzumab given with either chemotherapy or antiestrogen breast cancer should not be routinely performed and therapy, depending on the hormone receptor status of the should be guided by a patient’s symptoms or findings cancer and disease sites. First-line treatment with dual HER2- on examination that raise concern for recurrence. targeted therapy with trastuzumab and pertuzumab added to e Patients taking tamoxifen should have yearly gyneco- the taxane docetaxel has been shown to improve overall sur- logic examinations because of the increased risk of vival, with median overall survival of 56 months in a phase III endometrial cancer, and those on an aromatase inhibi- clinical trial. Ado-trastuzumab emtansine is commonly used tor should have bone density studies every other year to as a second-line treatment but may be used as first-line ther- assess osteoporosis. apy following a treatment-free interval of less than 6 months from adjuvant trastuzumab. Patients with triple-negative breast cancers (TNBC have a Metastatic Breast Cancer higher relapse rate than individuals with hormone receptor- Approximately 5% of patients with breast cancer present with positive cancers; recur earlier, with a peak at 3 years after diag- metastatic disease, and up to 30% with early-stage disease nosis and a very low risk of relapse after 5 years; and have a develop metastases. Metastatic breast cancer is not curable, but higher risk of locoregional recurrence and brain and lung systemic therapy can improve survival, relieve symptoms, and metastases. Advanced TNBC has historically been treated with maintain quality of life. Treatment and prognosis are related to chemotherapy. The addition of atezolizumab, a monoclonal whether visceral metastases are present, the number of sites antibody targeting programmed death ligand 1, to nab- involved, the interval between initial diagnosis and metastases paclitaxel improved overall survival (23.1 vs 17.6 months) for (intervals of less than 2 years have a poorer prognosis), the patients with programmed death ligand 1-positive metastatic patient’s performance status, and tumor biology. The median TNBC. TNBC may also be particularly responsive to platinum overall survival for patients with metastatic breast cancer is agents, particularly in BRCA mutation carriers. In patients with longer for women with hormone receptor-positive cancer or germline BRCA1 or BRCA2 mutations, poly (ADP-ribose) poly- HER2-positive cancer, some of whom may have prolonged merase inhibitors (olaparib, talazoparib) improve progression- survival, in part related to more treatment options. free survival relative to single-agent chemotherapy. These When evaluating a patient with newly diagnosed meta- agents cause “synthetic lethality” by producing an increase in static breast cancer, the lesion that upstages the patient to the double-strand DNA breaks that would usually be repaired by greatest degree should be biopsied. It is also important to the BRCA pathway. biopsy a site of initial metastasis both to confirm the diagnosis Chemotherapy agents used in patients with advanced and to assess hormone receptor and HER2 status, as there may breast cancer include taxanes, capecitabine, eribulin, gemcit- be treatment altering discordance in the receptors in the meta- abine, vinorelbine, ixabepilone, and liposomal doxorubicin. static lesion compared with the primary breast cancer in 10% Single-agent chemotherapy is usually given, with combination to 15% of patients. chemotherapy reserved for patients with extensive visceral In postmenopausal women with hormone receptor-pos- itive, HER2-negative breast cancer, endocrine-based therapy metastases where a higher response rate is important. is usually the initial treatment. In patients with rapidly pro- For all subtypes of breast cancer with bone metastases, gressive disease or extensive visceral metastases, initial che- bone-modifying agents such as zoledronic acid or deno-

aromatase inhibitor improves the response rate and duration of response to hormonal therapy. These drugs have been incor- e After completing treatment for breast cancer, follow-up porated into routine care for the majority of women with monitoring should be every 3 to 6 months for the first metastatic estrogen receptor-positive/ HER2-negative breast 3 years, every 6 to 12 months for the next 2 years, and cancer. then every year, with annual mammography for all survi- For patients with HER2-positive advanced breast cancer, vors, and breast MRI for those at high risk of recurrence. treatment should include HER2-directed therapy such as tras- HVC e Surveillance blood tests and other imaging tests for tuzumab given with either chemotherapy or antiestrogen breast cancer should not be routinely performed and therapy, depending on the hormone receptor status of the should be guided by a patient’s symptoms or findings cancer and disease sites. First-line treatment with dual HER2- on examination that raise concern for recurrence. targeted therapy with trastuzumab and pertuzumab added to e Patients taking tamoxifen should have yearly gyneco- the taxane docetaxel has been shown to improve overall sur- logic examinations because of the increased risk of vival, with median overall survival of 56 months in a phase III endometrial cancer, and those on an aromatase inhibi- clinical trial. Ado-trastuzumab emtansine is commonly used tor should have bone density studies every other year to as a second-line treatment but may be used as first-line ther- assess osteoporosis. apy following a treatment-free interval of less than 6 months from adjuvant trastuzumab. Patients with triple-negative breast cancers (TNBC have a Metastatic Breast Cancer higher relapse rate than individuals with hormone receptor- Approximately 5% of patients with breast cancer present with positive cancers; recur earlier, with a peak at 3 years after diag- metastatic disease, and up to 30% with early-stage disease nosis and a very low risk of relapse after 5 years; and have a develop metastases. Metastatic breast cancer is not curable, but higher risk of locoregional recurrence and brain and lung systemic therapy can improve survival, relieve symptoms, and metastases. Advanced TNBC has historically been treated with maintain quality of life. Treatment and prognosis are related to chemotherapy. The addition of atezolizumab, a monoclonal whether visceral metastases are present, the number of sites antibody targeting programmed death ligand 1, to nab- involved, the interval between initial diagnosis and metastases paclitaxel improved overall survival (23.1 vs 17.6 months) for (intervals of less than 2 years have a poorer prognosis), the patients with programmed death ligand 1-positive metastatic patient’s performance status, and tumor biology. The median TNBC. TNBC may also be particularly responsive to platinum overall survival for patients with metastatic breast cancer is agents, particularly in BRCA mutation carriers. In patients with longer for women with hormone receptor-positive cancer or germline BRCA1 or BRCA2 mutations, poly (ADP-ribose) poly- HER2-positive cancer, some of whom may have prolonged merase inhibitors (olaparib, talazoparib) improve progression- survival, in part related to more treatment options. free survival relative to single-agent chemotherapy. These When evaluating a patient with newly diagnosed meta- agents cause “synthetic lethality” by producing an increase in static breast cancer, the lesion that upstages the patient to the double-strand DNA breaks that would usually be repaired by greatest degree should be biopsied. It is also important to the BRCA pathway. biopsy a site of initial metastasis both to confirm the diagnosis Chemotherapy agents used in patients with advanced and to assess hormone receptor and HER2 status, as there may breast cancer include taxanes, capecitabine, eribulin, gemcit- be treatment altering discordance in the receptors in the meta- abine, vinorelbine, ixabepilone, and liposomal doxorubicin. static lesion compared with the primary breast cancer in 10% Single-agent chemotherapy is usually given, with combination to 15% of patients. chemotherapy reserved for patients with extensive visceral In postmenopausal women with hormone receptor-pos- itive, HER2-negative breast cancer, endocrine-based therapy metastases where a higher response rate is important. is usually the initial treatment. In patients with rapidly pro- For all subtypes of breast cancer with bone metastases, gressive disease or extensive visceral metastases, initial che- bone-modifying agents such as zoledronic acid or deno- motherapy may be used because of its higher response rate. sumab are recommended to decrease fractures, pain, and

is usually the initial treatment. In patients with rapidly pro- For all subtypes of breast cancer with bone metastases, gressive disease or extensive visceral metastases, initial che- bone-modifying agents such as zoledronic acid or deno- motherapy may be used because of its higher response rate. sumab are recommended to decrease fractures, pain, and Aromatase inhibitors are superior to other agents as first-line need for irradiation. Palliative irradiation can be used to treatment. Fulvestrant, which inhibits estrogen receptor treat painful bone metastases as well as other sites of tumor- function, and tamoxifen are other options. Premenopausal related pain or obstruction. Patients with TNBC and HER2- women can receive tamoxifen or ovarian suppression com- positive cancers have a higher risk of brain metastases, bined with either tamoxifen or aromatase inhibitors as initial which are treated with surgery, stereotactic irradiation, or treatment. whole brain irradiation. Palliative care teams can be helpful The addition of CDK4/6 inhibitors (abemaciclib, palboci- for managing symptoms of pain, nausea, anorexia, and clib, ribociclib) to aromatase inhibitors as first-line endocrine fatigue. Throughout the course of advanced breast cancer, therapy or to fulvestrant following progression on an discussions with patients about their goals of care should 13