Medication Summary
Adjuvant treatment for breast cancer involves radiation therapy and a variety of chemotherapeutic and biologic agents. It is designed to treat micrometastatic disease (or breast cancer cells that have escaped the breast and regional lymph nodes but which have not yet had an established identifiable metastasis). Treatment is aimed at reducing the risk of future recurrence, thereby reducing breast cancer−related morbidity and mortality. In patients with metastatic breast cancer, interventions include hormone therapy; chemotherapy; and biologic therapy targeted to the histologic and mutational characteristics of the tumor.
In patients receiving adjuvant aromatase inhibitor therapy for breast cancer who are at high risk for fracture, the monoclonal antibody denosumab or either of the bisphosphonates zoledronic acid and pamidronate may be added to the treatment regimen to increase bone mass. These agents are given along with calcium and vitamin D supplementation.
Antineoplastics, Alkylating
Class Summary
Alkylating agents constitute one of the earliest classes of antineoplastic agents used to treat cancer. They work by cross-linking DNA, which impedes cellular growth. They can be used alone or in combination with other chemotherapeutic agents.
Carboplatin
Carboplatin is an analogue of cisplatin. It is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA cross-links and inhibition of DNA replication. It binds to protein and other compounds containing the SH group. Cytotoxicity can occur at any stage of the cell cycle, but the cell is most vulnerable to the action of these drugs in the G1 and S phases.
Carboplatin has the same efficacy as cisplatin but a better toxicity profile. Its main advantages over cisplatin include less nephrotoxicity and ototoxicity, absence of a need for extensive prehydration, and reduced likelihood of inducing nausea and vomiting; however, it is more likely to induce myelotoxicity.
Cyclophosphamide (Cytoxan)
Cyclophosphamide is chemically related to nitrogen mustards. It can be used as a single agent or in various combination chemotherapy regimens for recurrent or metastatic breast cancer.
Cyclophosphamide is activated in the liver to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none type of reaction. The mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells.
Antineoplastics, Anthracycline
Class Summary
Anthracyclines work in multiple ways, including intercalation between DNA base pairs and inhibition of type II topoisomerase function, resulting in inhibition of cell replication and transcription. They also work by inhibition of DNA helicase, resulting in DNA cleavage.
Doxorubicin
Doxorubicin is a cytotoxic anthracycline that inhibits topoisomerase II and produces free radicals, which may cause destruction of DNA. It blocks DNA and RNA synthesis by inserting between adjacent base pairs and binding to the sugar-phosphate backbone of DNA, which causes DNA polymerase inhibition. It binds to nucleic acids, presumably by specific intercalation of the anthracycline nucleus with the DNA double helix.
This agent is also a powerful iron chelator. The iron-doxorubicin complex induces production of free radicals that can destroy DNA and cancer cells. Maximum toxicity occurs during the S phase of the cell cycle.
Epirubicin (Ellence)
Epirubicin is indicated as a part of adjuvant therapy in patients with evidence of axillary-node tumor involvement after resection of primary breast cancer. [142] It can be used as a single agent, but such use is much less common in the setting of recurrent or metastatic disease. Epirubicin is a cell cycle phase inhibitor–nonspecific anthracycline derivative of doxorubicin with maximum cytotoxic effects on the S and G2 phases of the cell cycle.
Calcium Metabolism Modifiers
Class Summary
Bisphosphonates are complementary to chemotherapy and hormone therapy because they may lessen the damage to bone from metastatic disease. Bisphosphonates inhibit osteoclast function and reduce the resorption of bone. An intravenous bisphosphonate should be used in combination with oral calcium citrate and vitamin D supplementation in bone metastasis, according to the National Comprehensive Cancer Network (NCCN) guidelines. [72]
Pamidronate (Aredia)
Pamidronate disodium is a bone resorption inhibitor that absorbs calcium phosphate crystals and prevents the dissolution of this mineral. It also inhibits osteoclast activity in the bone.
Zoledronic Acid (Zometa, Reclast)
Zoledronic acid inhibits bone resorption by acting on osteoclasts or osteoclast precursors. It may be superior to pamidronate in patients with lytic bone metastases.
Antineoplastics, Antimetabolite
Class Summary
Antimetabolite therapy can stop cancer cell growth and cell division by interfering with DNA replication of these cells. These drugs are often first-line agents for breast cancer.
Capecitabine (Xeloda)
Capecitabine is a pyrimidine analogue that, in combination with docetaxel, is indicated for metastatic breast cancer after the failure of prior anthracycline-containing chemotherapy.
Monotherapy with capecitabine is indicated for the treatment of patients with metastatic breast cancer that either is resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or is resistant to paclitaxel in a situation where further anthracycline therapy is not indicated. [143] It is the preferred first-line agent for human epidermal growth receptor 2 (HER2)-positive disease, along with trastuzumab.
Gemcitabine (Gemzar)
Gemcitabine is a pyrimidine analogue that is metabolized intracellularly to an active nucleotide. It inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. It is cell-cycle specific for the S phase. Gemcitabine, in combination with paclitaxel, is indicated as a first-line treatment for metastatic breast cancer after the failure of prior anthracycline-containing adjuvant chemotherapy (unless anthracyclines were clinically contraindicated).
Methotrexate (Trexall)
Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and cell reproduction in malignant cells. Methotrexate is indicated alone or in combination with other anticancer agents for the treatment of breast cancer.
Antineoplastics, Vinca Alkaloid
Class Summary
Monoclonal antibodies have been engineered to react against specific antigens on cancer cells, thereby potentially helping to enhance the patient’s immune response and prevent cancer cell growth.
Vinorelbine (Navelbine)
Vinorelbine is a semisynthetic vinca alkaloid that inhibits tubulin polymerization during the G2 phase of cell division, thereby inhibiting mitosis. This agent is a preferred first-line agent, with trastuzumab, for HER2-positive breast cancer. It is also used alone to treat recurrent or metastatic disease.
Monoclonal Antibodies
Class Summary
Monoclonal antibodies have been engineered to react against specific antigens on cancer cells, which can help to enhance the patient’s immune response and prevent cancer cell growth. The combination of both HER2 receptor antibodies (pertuzumab plus trastuzumab) is superior to either agent alone.
ado-trastuzumab emtansine (Kadcyla)
Ado-trastuzumab emtansine is an HER2-targeted antibody (trastuzumab) covalently linked to a microtubule inhibitor (DM1, a maytansine derivative). It is indicated for the treatment of HER2-positive metastatic breast cancer after prior trastuzumab and taxane therapy. It is also indicated for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane- and trastuzumab-based treatment.
Upon binding to sub-domain IV of the HER2 receptor, ado-trastuzumab emtansine undergoes receptor-mediated internalization and subsequent lysosomal degradation, resulting in intracellular release of DM1-containing cytotoxic catabolites. Binding of DM1 to tubulin disrupts microtubule networks in the cell, which results in cell cycle arrest and apoptotic cell death
Denosumab (Prolia, Xgeva)
Denosumab is a monoclonal antibody that specifically targets RANK ligand, an essential regulator of osteoclasts. This agent is indicated to prevent skeletal-related events (ie, bone fractures, spinal cord compression, or hypercalcemia) in patients with bone metastases from solid tumors whose expected survival exceeds 3 months.
Osteonecrosis of the jaw in patients receiving denosumab has often been associated with dental procedures. Consequently, patients should undergo a dental examination before the initiation of denosumab therapy to determine whether they might benefit from preventive dentistry procedures.
Trastuzumab (Herceptin, Ogivri, Herzuma, Ontruzant, Trazimera, trastuzumab-dkst, trastuzumab-pkrb, trastuzumab-dttb, trastuzumab-qyyp)
Trastuzumab is a monoclonal antibody that binds to extracellular HER2. It mediates antibody-dependent cellular cytotoxicity against cells that overproduce HER2.
It is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature) breast cancer, as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel, as part of a treatment regimen with docetaxel and carboplatin, or as a single agent following multimodality anthracycline based therapy. This agent is also used for HER2-overexpressing metastatic breast cancer as first-line treatment in combination with paclitaxel OR as a single agent for patients who have received 1 or more chemotherapy regimens for metastatic disease.
The combination of trastuzumab and an anthracycline is associated with significant cardiac toxicity.
Pertuzumab (Perjeta)
Pertuzumab is a monoclonal antibody that binds to the extracellular domain of the HER2 receptor. It is indicated for use in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. It is also the first drug approved for the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either >2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer . Pertuzumab was also indicated the adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence.
Trastuzumab/hyaluronidase (Herceptin Hylecta)
Trastuzumab is a monoclonal antibody which binds to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER-2). It mediates antibody-dependent cellular cytotoxicity by inhibiting proliferation of cells which overexpress HER-2 protein. It is indicated in combination with chemotherapy in patients with HER2-positive early breast cancer, in combination with paclitaxel in patients with metastatic HER2-positive breast cancer as a frontline treatment, and alone for patients with metastatic disease who have received at least 1 prior chemotherapy regimen. Administered SC over 2-5 minutes.
Trastuzumab deruxtecan (Enhertu, fam-trastuzumab deruxtecan-nxki)
HER2-targeted antibody-drug conjugate (ADC) which contains the humanized anti-HER2 IgG1, trastuzumab, covalently linked to the topoisomerase I inhibitor, deruxtecan. It is indicated for unresectable or metastatic HER2-positive breast cancer in adults who have received 2 or more prior anti-HER2-based regimens in the metastatic setting.
Sacituzumab govitecan (Sacituzumab govitecan-hziy, Trodelvy)
Sacituzumab govitecan is an antibody-drug conjugate that is directed against Trop-2 and binds to Trop-2 and delivers the anti-cancer drug, SN-38, to kill cancer cells. FDA granted accelerated approval to the first antibody drug conjugate for metastatic TNBC in patients who received at least two prior therapies for metastatic disease.
Pertuzumab/trastuzumab/hyaluronidase (Pertuzumab-trastuzumab-hyaluronidase-zzxf, Phesgo)
Pertuzumab/trastuzumab/hyaluronidase is a fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase administered as a subcutaneous injection. It is indicated in combination with IV chemotherapy, for the treatment of early and metastatic HER2-positive breast cancer.
Tyrosine Kinase Inhibitors
Class Summary
Tyrosine kinase inhibitors play an important role in the modulation of growth factor signaling. They are commonly combined with other forms of chemotherapy or radiation therapy.
Lapatinib (Tykerb)
Lapatinib is a 4-anilinoquinazoline kinase that inhibits the intracellular tyrosine kinase domains of epidermal growth factor receptor (EGFR [ErbB1]) and HER2 (ErbB2). This agent is indicated in combination with capecitabine for advanced or metastatic breast cancer in patients with tumors that overexpress HER2 and for which previous therapy (ie, anthracycline, taxane, and trastuzumab) was not effective.
This agent is also used in combination with letrozole for the treatment of postmenopausal women with hormone receptor–positive metastatic breast cancer tumors that overexpress the HER2 receptor, for whom hormonal therapy is indicated. [145]
Neratinib (Nerlynx)
Tyrosine kinase inhibitor indicated for extended adjuvant therapy following trastuzumab-based therapy with early stage HER2 overexpressed/amplified breast cancer. It irreversibly binds to EGFR, HER2, and HER4. In vitro, inhibition reduces EGFR and HER2 autophosphorylation, subsequently inhibits signal transduction pathways and demonstrates antitumor activity in overexpressed EGFR and/or HER2 carcinoma cells; neratinib human metabolites (M3, M6, M7, and M11) inhibits EGFR, HER2 and HER4 activity.
Tucatinib (Tukysa)
Tucatinib (tyrosine kinase inhibitor or HER2) inhibits phosphorylation of HER2 and HER3, ultimately inhibiting MAPK and AKT signaling and cell proliferation and antitumor activity in HER2 expressing tumor cells. It is indicated in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.
Antineoplastics, Antimicrotubular
Class Summary
Use of antimicrotubular therapy may be considered in patients who have received at least 2 chemotherapeutic regimens for metastatic disease.
Eribulin (Halaven)
Eribulin inhibits the growth phase of microtubules, leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death. It is indicated for metastatic breast cancer in patients who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or the metastatic setting.
Docetaxel (Taxotere, Docefrez)
Docetaxel is indicated for use in combination with doxorubicin and cyclophosphamide for adjuvant treatment of operable node-positive breast cancer. It is also indicated for locally advanced or metastatic breast cancer after failure of prior chemotherapy. It is a semisynthetic taxane, a class of drugs that inhibits cancer cell growth by promoting assembly and blocking the disassembly of microtubules, thereby preventing cancer cell division and leading to cell death.
Paclitaxel (Taxol)
Paclitaxel is indicated for adjuvant treatment of node-positive breast cancer; it is administered sequentially after doxorubicin-containing combination chemotherapy. Dose-dense regimens (ie, more frequent administration) are currently being studied and resulting disease-free interval examined. Mechanisms of action are tubulin polymerization and microtubule stabilization, which, in turn, inhibit mitosis and may result in the breakage of chromosomes.
Ixabepilone (Ixempra)
Ixabepilone is a semisynthetic analogue of epothilone B that inhibits microtubules, halting cell division in the mitotic phase and resulting in cell death. It is used mostly in combination with capecitabine in patients with recurrent or metastatic breast cancer in whom therapy with other first-line agents (eg, an anthracycline and a taxane) has failed.
Aromatase Inhibitors
Class Summary
Aromatase inhibitors play a role in adjuvant therapy in breast cancer. These agents work by inhibiting aromatase, the enzyme responsible for converting other steroid hormones into estrogen. All 3 selective aromatase inhibitors (anastrozole, letrozole, and exemestane) have similar antitumor efficacy and similar toxicity profiles.
Anastrozole (Arimidex)
Anastrozole significantly lowers serum estradiol concentrations by inhibiting the conversion of adrenally generated androstenedione to estrone. It is used as first-line treatment of breast cancer in postmenopausal women with hormone receptor–positive or hormone receptor–unknown locally advanced or metastatic disease. It is also used to treat advanced breast cancer in postmenopausal women with disease progression after tamoxifen therapy.
Letrozole (Femara)
Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system. It inhibits the conversion of androgens to estrogens. Letrozole is indicated for adjuvant treatment of postmenopausal women with hormone receptor–positive early breast cancer. It is also used for first-line treatment of postmenopausal women with hormone receptor–positive or hormone receptor–unknown locally advanced or metastatic breast cancer.
Letrozole is also indicated for treatment of advanced breast cancer in postmenopausal women with disease progression after antiestrogen therapy and for extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy. [146]
Exemestane (Aromasin)
Exemestane elicits irreversible steroidal aromatase inactivation by acting as a false substrate for the aromatase enzyme. It binds irreversibly to the aromatase enzyme active site, causing inactivation (ie, suicide inhibition). It significantly lowers circulating estrogen concentrations in postmenopausal women.
Exemestane differs from tamoxifen in that it inhibits estrogen production, whereas tamoxifen inhibits estrogen at the receptor site. It may be superior to tamoxifen for breast cancer chemoprevention, with a better safety profile. However, exemestane is not yet indicated for this application by the American Society of Clinical Oncology (ASCO). It is indicated for advanced breast cancer in postmenopausal women whose disease has progressed after tamoxifen therapy. Off-label use of exemestane is suggested as an alternative to tamoxifen or raloxifene in the 2013 ASCO guidelines to reduce the risk of ER-positive breast cancer in high-risk postmenopausal women. [135]
CDK Inhibitors
Class Summary
Palbociclib and ribociclib are cyclin-dependent kinases (CDK) 4, 6 inhibitors indicated in combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.
Palbociclib (Ibrance)
Palbociclib is a cyclin dependent kinases (CDK) 4, 6 inhibitor. It reduces cellular proliferation of ER-positive breast cancer cell lines by blocking progression of the cell from G1 into S phase of the cell cycle. It is indicated in combination with letrozole for treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. It is also approved for ER+/HER2- advanced breast cancer in combination with fulvestrant in women (regardless of menopausal status) with disease progression following endocrine therapy.
Ribociclib (Kisqali)
CDK 4, 6 inhibitor. CDK inhibitors block cellular proliferation of G1 into S phase of the cell cycle. It is indicated in combination with an aromatase inhibitor (eg, letrozole) as initial endocrine-based therapy for postmenopausal women with HR+/HER- advanced or metastatic breast cancer.
Abemaciclib (Verzenio)
CDK 4, 6 inhibitor. These kinases are activated upon binding to D cyclins and play a crucial role in signaling pathways which lead to cell cycle progression and cellular proliferation. In ER-positive breast cancer cells, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation. It is indicated for HR+/HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy as either monotherapy or in combination with fulvestrant. It is also indication for the frontline treatment of postmenopausal women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor.
Antineoplastics, PARP Inhibitors
Class Summary
This class of agents is thought to augment cytotoxic therapy without increasing adverse effects and to kill cancer cells with DNA repair defects as a single agent. The genomic instability of some tumor cells allows poly (ADP-ribose) polymerase (PARP) inhibitors to have selectivity for the tumor cells over normal cells.
Olaparib was the first PARP inhibitor approved for breast cancer. Its approval was based on the first phase 3 randomized trial that demonstrated PARP inhibitors were superior to chemotherapy for patients with HER2-negative metastatic breast cancer with a BRCA mutation. [173]
Olaparib (Lynparza)
Indicated for deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, in patients who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. It also indicated for adjuvant treatment of deleterious or suspected deleterious gBRCAm HER2-negative high-risk early breast cancer in adults previously treated with neoadjuvant or adjuvant chemotherapy.
Talazoparib (Talzenna)
Indicated for patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer.
Antineoplastics, Estrogen Receptor Antagonist
Class Summary
Selective estrogen receptor modulators (SERMs) stimulate or inhibit the estrogen receptors of various target tissues.
Tamoxifen (Soltamox)
Tamoxifen is a nonsteroid with potent antiestrogenic effects in the breast; however, it may be an estrogen agonist in the uterus. CYP2C19 heterozygous*2 carriership may be a predictive factor for longer survival in patients with breast cancer who are taking tamoxifen. [147] Tamoxifen is considered the gold standard for prevention of breast cancer in high-risk women, as adjuvant treatment for breast cancer, and in metastatic breast cancer.
Raloxifene (Evista)
Raloxifene is a selective nonsteroidal benzothiophene ER modulator. It is indicated for reducing the risk of invasive breast cancer in postmenopausal women with osteoporosis. In addition, it is indicated for risk reduction in postmenopausal women at high risk for invasive breast cancer.
Toremifene (Fareston)
Toremifene is a nonsteroidal triphenylethylene derivative that binds to estrogen receptors. It may exert estrogenic activities, antiestrogenic activities, or both. It is indicated for metastatic breast cancer in postmenopausal women with ER-positive or ER-unknown tumors. [148]
Elacestrant (Orserdu)
Indicated for men or postmenopausal women with estrogen receptor positive (ER+), HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least 1 line of endocrine therapy.
PD-1/PD-L1 Inhibitors
Class Summary
PD-L1 is expressed on the surface of activated T cells under normal conditions; binding PDL1 inhibits immune activation and reduces T-cell cytotoxic activity when bound. This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation. Tumor cells may circumvent T-cell–mediated cytotoxicity by expressing PDL1 on the tumor itself or on tumor-infiltrating immune cells, resulting in the inhibition of immune-mediated killing of tumor cells.
Atezolizumab (Tecentriq)
Monoclonal antibody to programmed cell death ligand-1 protein (PDL1). It blocks the interaction between PDL-1 and its ligands. It is indicated in combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells of any intensity covering ≥11% of the tumor area), as defined by an FDA-approved test.
PI3K Inhibitors
Alpelisib (Piqray)
PI3K inhibitor indicated in combination with fulvestrant for treatment of men and postmenopausal women with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen.
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Anatomy of the breast.
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Intrinsic subtypes of breast cancer.
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Breast cancer. Intraductal carcinoma, comedo type. Distended duct with intact basement membrane and central tumor necrosis.
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Breast cancer. Intraductal carcinoma, noncomedo type. Distended duct with intact basement membrane, micropapillary, and early cribriform growth pattern.
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Breast cancer. Lobular carcinoma in situ. Enlargement and expansion of lobule with monotonous population of neoplastic cells.
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Breast cancer. Lobular carcinoma in situ. Enlargement and expansion of lobule with monotonous population of neoplastic cells.
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Breast cancer. Infiltrating ductal carcinoma. Low-grade carcinoma with well-developed glands invading fibrous stroma.
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Breast cancer. Colloid (mucinous) carcinoma. Nests of tumor cells in pool of extracellular mucin.
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Breast cancer. Papillary carcinoma. Solid papillary growth pattern with early cribriform and well-developed thin papillary fronds.
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Anatomy of the breast. Courtesy of Wikimedia Commons (Patrick J Lynch, medical illustrator).
Tables
- Table 1. Accuracy of Breast Imaging Modalities
- Table 2. Grading System in Invasive Breast Cancer (Modified Bloom and Richardson)
- Table 3. Ductal Carcinoma in Situ Subtypes
- Table 4. TNM Classification for Breast Cancer
- Table 5. Histologic grade
- Table 6. Anatomic stage/prognostic groups
- Table 7. Clinical prognostic stage
- Table 8. Pathological prognostic stage
- Table 9. Hormone Agents Used in Breast Cancer
- Table 10. Targeted Chemotherapy for Metastatic Breast Cancer
- Table 11. Combination Regimens for Metastatic Breast Cancer
- Table 12. Follow-up Recommendations for Breast Cancer Survivors
- Table 13.
Modality |
Sensitivity |
Specificity |
PPV |
Indications |
Mammography |
63-95% (>95% palpable, 50% impalpable, 83-92% in women older than 50 y; decreases to 35% in dense breasts) |
14-90% (90% palpable) |
10-50% (94% palpable) |
Initial investigation for symptomatic breast in women older than 35 y and for screening; investigation of choice for microcalcification |
Ultrasonography |
68-97% palpable |
74-94% palpable |
92% (palpable) |
Initial investigation for palpable lesions in women younger than 35 y |
MRI |
86-100% |
21-97% (< 40% primary cancer) |
52% |
Scarred breast, implants, multifocal lesions, and borderline lesions for breast conservation; may be useful in screening high-risk women |
Scintigraphy |
76-95% palpable, 52-91% impalpable |
62-94% (94% impalpable) |
70-83% (83% palpable, 79% impalpable) |
Lesions >1 cm and axilla assessment; may help predict drug resistance |
PET |
96% (90% axillary metastases) |
100% |
|
Axilla assessment, scarred breast, and multifocal lesions |
MRI = magnetic resonance imaging; PET = positron emission tomography; PPV = positive predictive value. |
||||
|
Score |
||
|
1 |
> 2 |
> 3 |
A. Tubule formation |
>75% |
10-75% |
< 10% |
B. Mitotic count/HPF (microscope- and field-dependent) |
< 7 |
7-12 |
>12 |
C. Nuclear size and pleomorphism |
Near normal; little variation |
Slightly enlarged; moderate variation |
Markedly enlarged; marked variation |
Grade I cancer if total score (A + B + C) is 3-5 |
|||
Grade II cancer if total score (A + B + C) is 6 or 7 |
|||
Grade III cancer if total score (A + B + C) is 8 or 9 |
|||
HPF = high-power field. |
|||
DCIS Characteristic |
Comedo |
Noncomedo |
Nuclear grade |
High |
Low |
Estrogen receptor |
Often negative |
Positive |
Distribution |
Continuous |
Multifocal |
Necrosis |
Present |
Absent |
Local recurrence |
High |
Low |
Prognosis |
Worse |
Better |
DCIS = ductal carcinoma in situ. |
||
Primary tumor (T) |
|
TX |
Primary tumor cannot be assessed |
T0 |
No evidence of primary tumor |
Tis |
Carcinoma in situ |
Tis (DCIS) |
Ductal carcinoma in situ |
Tis (Paget) |
Paget disease of the nipple NOT associated with invasive carcinoma and/or carcinoma in situ (DCIS) in the underlying breast parenchyma. Carcinomas in the breast parenchyma associated with Paget disease are categorized on the basis of the size and characteristics of the parenchymal disease, although the presence of Paget disease should still be noted |
T1 |
Tumor ≤ 20 mm in greatest dimension |
T1mi |
Tumor ≤ 1 mm in greatest dimension |
T1a |
Tumor > 1 mm but ≤ 5 mm in greatest dimension (round any measurement >1.0-1.9 mm to 2 mm) |
T1b |
Tumor > 5 mm but ≤ 10 mm in greatest dimension |
T1c |
Tumor > 10 mm but ≤ 20 mm in greatest dimension |
T2 |
Tumor > 20 mm but ≤ 50 mm in greatest dimension |
T3 |
Tumor > 50 mm in greatest dimension |
T4 |
Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules), not including invasion of dermis alone |
T4a |
Extension to chest wall, not including only pectoralis muscle adherence/invasion |
T4b |
Ulceration and/or ipsilateral satellite nodules and/or edema (including peau d’orange) of the skin, which do not meet the criteria for inflammatory carcinoma |
T4c |
Both T4a and T4b |
T4d |
Inflammatory carcinoma |
Regional lymph nodes (N) |
|
Clinical |
|
cNX |
Regional lymph nodes cannot be assessed (eg, previously removed) |
cN0 |
No regional lymph node metastasis (on imaging or clinical examination) |
cN1 |
Metastasis to movable ipsilateral level I, II axillary lymph node(s) |
cN1mi |
Micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm) |
cN2 |
Metastases in ipsilateral level I, II axillary lymph nodes that are clinically fixed or matted; or in ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastases |
cN2a |
Metastases in ipsilateral level I, II axillary lymph nodes fixed to one another (matted) or to other structures |
cN2b |
Metastases only in ipsilateral internal mammary nodes and in the absence of axillary lymph node metastases |
cN3 |
Metastases in ipsilateral infraclavicular (level III axillary) lymph node(s), with or without level I, II axillary node involvement, or in ipsilateral internal mammary lymph node(s) with level I, II axillary lymph node metastasis; or metastases in ipsilateral supraclavicular lymph node(s), with or without axillary or internal mammary lymph node involvement |
cN3a |
Metastasis in ipsilateral infraclavicular lymph node(s) |
cN3b |
Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) |
cN3c |
Metastasis in ipsilateral supraclavicular lymph node(s) |
Note: (sn) and (f) suffixes should be added to the N category to denote confirmation of metastasis by sentinel node biopsy or fine needle aspiration/core needle biopsy, respectively. |
|
Pathologic (pN) |
|
pNX |
Regional lymph nodes cannot be assessed (for example, previously removed, or not removed for pathologic study) |
pN0 |
No regional lymph node metastasis identified histologically, or isolated tumor cell clusters (ITCs) only. Note: ITCs are defined as small clusters of cells ≤ 0.2 mm, or single tumor cells, or a cluster of < 200 cells in a single histologic cross-section; ITCs may be detected by routine histology or by immunohistochemical (IHC) methods; nodes containing only ITCs are excluded from the total positive node count for purposes of N classification but should be included in the total number of nodes evaluated |
pN0(i) |
No regional lymph node metastases histologically, negative IHC |
pN0(i+) |
ITCs only in regional lymph node(s) |
pN0(mol-) |
No regional lymph node metastases histologically, negative molecular findings (reverse transcriptase polymerase chain reaction [RT-PCR]) |
pN0(mol+) |
Positive molecular findings by RT-PCR; no ITCs detected |
pN1 |
Micrometastases; or metastases in 1-3 axillary lymph nodes and/or in internal mammary nodes; and/or in clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy |
pN1mi |
Micrometastases (200 cells, > 0.2 mm but none > 2.0 mm) |
pN1a |
Metastases in 1-3 axillary lymph nodes (at least 1 metastasis > 2.0 mm) |
pN1b |
Metastases in ipsilateral internal mammary lymph nodes, excluding ITCs, detected by sentinel lymph node biopsy |
pN1c |
Metastases in 1-3 axillary lymph nodes and in internal mammary sentinel nodes (ie, pN1a and pN1b combined) |
pN2 |
Metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases |
pN2a |
Metastases in 4-9 axillary lymph nodes (at least 1 tumor deposit > 2.0 mm) |
pN2b |
Clinically detected* metastases in internal mammary lymph nodes with or without microscopic confirmation; with pathologically negative axillary lymph nodes |
pN3 |
Metastases in ≥ 10 axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive level I, II axillary lymph nodes; or in > 3 axillary lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes |
pN3a |
Metastases in ≥ 10 axillary lymph nodes (at least 1 tumor deposit > 2.0 mm); or metastases to the infraclavicular (level III axillary lymph) nodes |
pN3b |
pN1a or pN2a in the presence of cN2b (positive internal mammary nodes by imaging) or pN2a in the presence of pN1b |
pN3c |
Metastases in ipsilateral supraclavicular lymph nodes |
*"Clinically detected" is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination and having characteristics highly suspicious for malignancy or a presumed pathologic macrometastasis on the basis of FNA biopsy with cytologic examination. |
|
Distant metastasis (M) |
|
M0 |
No clinical or radiographic evidence of distant metastasis |
cM0(i+) |
No clinical or radiographic evidence of distant metastases in the presence of tumor cells or deposits no larger than 0.2 mm detected microscopically or by molecular techniques in circulating blood, bone marrow, or other nonregional nodal tissue in a patient without symptoms or signs of metastase |
cM1 |
Distant metastases detected by clinical and radiographic means |
pM1 |
Any histologically proven metastases in distant organs; or if in non-regional nodes, metastases > 0.2 mm |
Histologic grade (G) |
|
GX |
Grade cannot be assessed |
G1 |
Low combined histologic grade (favorable) |
G2 |
Intermediate combined histologic grade (moderately favorable) |
G3 |
High combined histologic grade (unfavorable) |
Stage |
T |
N |
M |
0 |
Tis |
N0 |
M0 |
IA |
T1 |
N0 |
M0 |
IB |
T0 |
N1mi |
M0 |
|
T1 |
N1mi |
M0 |
IIA |
T0 |
N1 |
M0 |
|
T1 |
N1 |
M0 |
|
T2 |
N0 |
M0 |
IIB |
T2 |
N1 |
M0 |
|
T3 |
N0 |
M0 |
IIIA |
T0 |
N2 |
M0 |
|
T1 |
N2 |
M0 |
|
T2 |
N2 |
M0 |
|
T3 |
N1 |
M0 |
|
T3 |
N2 |
M0 |
IIIB |
T4 |
N0 |
M0 |
|
T4 |
N1 |
M0 |
|
T4 |
N2 |
M0 |
IIIC |
Any T |
N3 |
M0 |
IV |
Any T |
Any N |
M1 |
TNM |
Grade |
HER2 |
ER |
PR |
Stage |
Tis N0 M0 |
Any |
Any |
Any |
Any |
0 |
T1 N0 M0 T0 N1mi M0 T1 N1mi M0 |
G1 |
Positive |
Positive |
Positive |
IA |
Negative |
|||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
|||
Negative |
|||||
Negative |
Positive |
||||
Negative |
IB |
||||
G2 |
Positive |
Positive |
Positive |
IA |
|
Negative |
|||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
|||
Negative |
|||||
Negative |
Positive |
||||
Negative |
IB |
||||
G3 |
Positive |
Positive |
Positive |
IA |
|
Negative |
|||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
|||
Negative |
IB |
||||
Negative |
Positive |
||||
Negative |
|||||
T0 N1 M0 T1 N1 M0 T2 N0 M0 |
G1 |
Positive |
Positive |
Positive |
IB |
Negative |
IIA |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
IB |
||
Negative |
IIA |
||||
Negative |
Positive |
||||
Negative |
|||||
G2 |
Positive |
Positive |
Positive |
IB |
|
Negative |
IIA |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
IB |
||
Negative |
IIA |
||||
Negative |
Positive |
||||
Negative |
IIB |
||||
G3 |
Positive |
Positive |
Positive |
IB IIA |
|
Negative |
|||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
|||
Negative |
IIB |
||||
Negative |
Positive |
||||
Negative |
|||||
T2 N1 M0 T3 N0 M0 |
G1 |
Positive |
Positive |
Positive |
IB |
Negative |
IIA |
||||
Negative |
Positive |
||||
Negative |
IIB |
||||
Negative |
Positive |
Positive |
IIA |
||
Negative |
IIB |
||||
Negative |
Positive |
||||
Negative |
|||||
G2 |
Positive |
Positive |
Positive |
IB |
|
Negative |
IIA |
||||
Negative |
Positive |
||||
Negative |
IIB |
||||
Negative |
Positive |
Positive |
IIA |
||
Negative |
IIB |
||||
Negative |
Positive |
||||
Negative |
IIIB |
||||
G3 |
Positive |
Positive |
Positive |
IB |
|
Negative |
IIB |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
|||
Negative |
IIIA |
||||
Negative |
Positive |
||||
Negative |
IIIB |
||||
T0 N2 M0 T1 N2 M0 T2 N2 M0 T3 N1 M0 T3 N2 M0 |
G1 |
Positive |
Positive |
Positive |
IIA |
Negative |
IIIA |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
IIA |
||
Negative |
IIIA |
||||
Negative |
Positive |
||||
Negative |
IIIB |
||||
G2 |
Positive |
Positive |
Positive |
IIA |
|
Negative |
IIIA |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
IIA |
||
Negative |
IIIA |
||||
Negative |
Positive |
||||
Negative |
IIIB |
||||
G3 |
Positive |
Positive |
Positive |
IIB |
|
Negative |
IIIA |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
|||
Negative |
IIIB |
||||
Negative |
Positive |
||||
Negative |
IIIC |
||||
T4 N0 M0 T4 N1 M0 T4 N2 M0 Any T N3 M0 |
G1 |
Positive |
Positive |
Positive |
IIIA |
Negative |
IIIB |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
|||
Negative |
|||||
Negative |
Positive |
||||
Negative |
IIIC |
||||
G2 |
Positive |
Positive |
Positive |
IIIA |
|
Negative |
IIIB |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
|||
Negative |
|||||
Negative |
Positive |
||||
Negative |
IIIC |
||||
G3 |
Positive |
Positive |
Positive |
IIIB |
|
Negative |
|||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
|||
Negative |
IIIC |
||||
Negative |
Positive |
||||
Negative |
|||||
Any T Any N M1 |
Any |
Any |
Any |
Any |
IV |
ER=estrogen receptor; PR=progesterone receptor |
|||||
TNM |
Grade |
HER2 |
ER |
PR |
Stage |
Tis N0 M0 |
Any |
Any |
Any |
Any |
0 |
T1 N0 M0 T0 N1mi M0 T1 N1mi M0 |
G1 |
Positive |
Positive |
Positive |
IA |
Negative |
|||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
|||
Negative |
|||||
Negative |
Positive |
||||
Negative |
|||||
G2 |
Positive |
Positive |
Positive |
||
Negative |
|||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
|||
Negative |
|||||
Negative |
Positive |
||||
Negative |
IB |
||||
G3 |
Positive |
Positive |
Positive |
IA |
|
Negative |
|||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
|||
Negative |
|||||
Negative |
Positive |
||||
Negative |
IB |
||||
T0 N1 M0 T1 N1 M0 T2 N0 M0 |
G1 |
Positive |
Positive |
Positive |
IA |
Negative |
IB |
||||
Negative |
Positive |
||||
Negative |
IIA |
||||
Negative |
Positive |
Positive |
IA |
||
Negative |
IB |
||||
Negative |
Positive |
||||
Negative |
IIA |
||||
G2 |
Positive |
Positive |
Positive |
IA |
|
Negative |
IB |
||||
Negative |
Positive |
||||
Negative |
IIA |
||||
Negative |
Positive |
Positive |
IA |
||
Negative |
IIA |
||||
Negative |
Positive |
||||
Negative |
|||||
G3 |
Positive |
Positive |
Positive |
IA IIA |
|
Negative |
|||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
IB |
||
Negative |
IIA |
||||
Negative |
Positive |
||||
Negative |
|||||
T2 N1 M0 T3 N0 M0 |
G1 |
Positive |
Positive |
Positive |
IA |
Negative |
IIB |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
IA |
||
Negative |
IIB |
||||
Negative |
Positive |
||||
Negative |
|||||
G2 |
Positive |
Positive |
Positive |
IB |
|
Negative |
IIB |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
IB |
||
Negative |
IIB |
||||
Negative |
Positive |
||||
Negative |
|||||
G3 |
Positive |
Positive |
Positive |
IB |
|
Negative |
IIB |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
IIA |
||
Negative |
IIB |
||||
Negative |
Positive |
||||
Negative |
IIIA |
||||
T0 N2 M0 T1 N2 M0 T2 N2 M0 T3 N1 M0 T3 N2 M0 |
G1 |
Positive |
Positive |
Positive |
IB |
Negative |
IIIA |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
IB |
||
Negative |
IIIA |
||||
Negative |
Positive |
||||
Negative |
|||||
G2 |
Positive |
Positive |
Positive |
IB |
|
Negative |
IIIA |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
IB |
||
Negative |
IIIA |
||||
Negative |
Positive |
||||
Negative |
IIIB |
||||
G3 |
Positive |
Positive |
Positive |
IIA |
|
Negative |
IIIA |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
IIA |
||
Negative |
IIIA |
||||
Negative |
Positive |
||||
Negative |
IIIC |
||||
T4 N0 M0 T4 N1 M0 T4 N2 M0 Any T N3 M0 |
G1 |
Positive |
Positive |
Positive |
IIIA |
Negative |
IIIB |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
IIIA |
||
Negative |
IIIB |
||||
Negative |
Positive |
||||
Negative |
|||||
G2 |
Positive |
Positive |
Positive |
IIIA |
|
Negative |
IIIB |
||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
IIIA |
||
Negative |
IIIB |
||||
Negative |
Positive |
||||
Negative |
IIIC |
||||
G3 |
Positive |
Positive |
Positive |
IIIB |
|
Negative |
|||||
Negative |
Positive |
||||
Negative |
|||||
Negative |
Positive |
Positive |
|||
Negative |
IIIC |
||||
Negative |
Positive |
||||
Negative |
|||||
Any T Any N M1 |
Any |
Any |
Any |
Any |
IV |
ER=estrogen receptor; PR=progesterone receptor |
|||||
Agent |
Dose and Schedule |
Postmenopausal |
|
Tamoxifen |
20 mg PO every day |
| Elacestrant | 345 mg PO every day |
Or |
|
Aromatase inhibitor |
|
Anastrozole |
1 mg PO every day |
Letrozole |
2.5 mg PO every day |
Exemestane |
25 mg PO every day |
Or |
|
Fulvestrant |
500 mg IM on days 1, 15, 29, and once monthly thereafter |
Or |
|
Megestrol |
40 mg PO 4 times a day |
Premenopausal |
|
Tamoxifen |
20 mg PO every day |
Or |
|
Aromatase inhibitor + LHRH* |
|
Leuprolide |
7.5 mg IM depot q28d 22.5 mg IM q3mo 30 mg IM q4mo |
Goserelin |
3.6 mg SC depot q28d 10.8 mg SC q3mo |
Megestrol |
40 mg PO 4 times a day |
*LHRH = luteinizing hormone–releasing hormone. |
|
Drug |
Class |
Dose/Schedule |
Overall Response Rate (ORR) |
Toxicity |
| Abemaciclib | CDK inhibitor | 200 mg PO BID continue until disease progression |
19.7% | Diarrhea, fatigue, neutropenia and nausea |
Capecitabine |
Oral fluoro-pyrimidine |
1250 mg/m²/d PO for 2 weeks with 1 wk off |
30% |
Rash, hand-foot syndrome, diarrhea, mucositis |
Docetaxel |
Antimicrotubule |
75-100 mg/m² IV q3wk or 40 mg/m²/wk X IV for 6 wk with 2 wk off |
30-68% |
Myelosuppression, alopecia, skin reaction, mucositis, and fluid retention |
Doxorubicin |
Anthracycline (antitumor antibiotic) |
45-60 mg/m² IV q3wk or 20 mg/m² IV qwk (not to exceed a cumulative dose of 450-500 mg/m²) |
35-50% |
Myelosuppression, nausea/ vomiting, mucositis, diarrhea cardiotoxicity, alopecia |
Doxil (liposomal encapsulated doxorubicin) |
Anthracycline |
20 mg/m² IV q2wk or 35-40 mg/m² IV q4wk |
|
Less cardiotoxicity, neutropenia, alopecia, stomatitis, hand-foot syndrome |
Epirubicin |
Anthracycline |
90 mg/m² IV q3wk (not to exceed cumulative dose of 900 mg/m²) |
35-50% |
Myelosuppression, mucositis, nausea, vomiting, cardiotoxicity |
Gemcitabine |
Antimetabolite |
725 mg/m²/wk IV for 3 wk then 1 wk off or 1 g/m²/wk IV X 2 then 1 wk off |
|
Myelosuppression, nausea/ vomiting, flulike syndrome, elevated LFTs |
Nab-paclitaxel |
Antimicrotubule |
80-100 mg/m²/wk IV X 3 then 1 wk off or 260 mg/m² IV q3wk |
58-62% 33% |
Less neuropathy, and allergic reaction |
| Olaparib | PARP inhibitor | 300 mg PO BID | 59.9% | Anemia, fatigue, nausea, and vomiting |
Paclitaxel |
Antimicrotubule |
80 mg/m²/wk IV or 175 mg/m² IV over 3 hours q3wk |
25-50% |
Myelosuppression, alopecia, neuropathy, allergic reaction |
Pertuzumab |
Monoclonal antibody |
840 mg IV loading dose, then 420 mg q3wk Give with trastuzumab and docetaxel |
80.2% (objective response rate) |
Fever, allergic reaction, cardiotoxicity/congestive heart failure |
Palbociclib |
CDK inhibitor |
125 mg/day PO for 3 weeks with 1 wk off Give with letrozole |
Data are not available for ORR Mean PFS was 10.2 months in the letrozole group and 20.2 months for palbociclib plus letrozole group |
Neutropenia, leukopenia, thrombocytopenia, anemia, stomatitis |
| Ribociclib | CDK inhibitor | 600 mg/day PO for 3 weeks with 1 wk off Give with letrozole |
Mean PFS was 16 months in the letrozole group and 25.3 months for ribociclib | QT prolongation, hepatobiliary toxicity, neutropenia, alopecia, diarrhea, vomiting, constipation, fatigue, anorexia |
| Sacituzumab govitecan | Monoclonal antibody | 10 mg/kg IV on Days 1 and 8 with 2 wk off | 33.3% | Nausea, neutropenia, diarrhea, fatigue, anemia, vomiting |
| Talazoparib | PARP inhibitor | 1 mg PO qDay | 62.6% | Fatigue, anemia, nausea, neutropenia, headache, thrombocytopenia, vomiting, alopecia, diarrhea, and decreased appetite |
Trastuzumab or biosimilars of trastuzumab |
Monoclonal antibody | Combination therapy: 4 mg/kg IV once, then 2 mg/kg weekly for 12-18 weeks, then 6 mg/kg q3weeks to total 52 weeks Single agent: 8 mg/kg IV once, then 6 mg/kg q3weeks to total 52 weeks |
10-15% | Fever, allergic reaction, cardiotoxicity/congestive heart failure |
| Trastuzumab deruxtecan [155] | Monoclonal antibody conjugate | 5.4 mg/kg IV q3weeks | 60.3% | Interstitial lung disease and pneumonitis; neutropenia; left ventricular dysfunction |
| Tucatinib [156] | Tyrosine kinase inhibitor of HER2 | 300 mg PO BID | 40.6% | Diarrhea, hand-foot syndrome, nausea, fatigue, hepatotoxicity |
Vinorelbine |
Vinca alkaloid |
20 mg/m²/wk IV |
35-45% |
Myelosuppression, nausea/ vomiting, constipation, fatigue, stomatitis, anorexia |
Chemotherapy |
Dose and Schedule |
Cycle |
XT |
||
Capecitabine Docetaxel |
1250 mg/m² bid days 1-14 75 mg/m² day 1 |
Repeat cycle every 21 days May decrease capecitabine dose to 850-1000 mg/m² to reduce toxicity risk |
XP |
||
Capecitabine Paclitaxel |
825 mg/m² bid days 1-14 175 mg/m² day 1 |
Repeat cycle every 21 days |
XN |
||
Capecitabine Navelbine |
1000 mg/m² bid days 1-14 25 mg/m² days 1 and 8 |
Repeat cycle every 21 days |
Gemcitabine [157] Paclitaxel |
1250 mg/m² days 1 and 8 175 mg/m² day 1 |
Repeat cycle every 21 days |
Carboplatin [158] Paclitaxel |
AUC of 6 day 1 200 mg/m² day 1 |
Repeat cycle every 21 days |
Carboplatin [159] Docetaxel |
AUC of 6 day 1 75 mg/m² day 1 |
Repeat cycle every 21 days |
Palbociclib [149] Letrozole |
125 mg PO once daily days 1-21 2.5 mg PO once daily days 1-28 |
Repeat cycle every 28 days |
Palbociclib Fulvestrant |
125 mg PO once daily days 1-21 500 mg IM on days 1, 15, 29 and once monthly thereafter |
Repeat cycle every 28 days |
Ribociclib [151] Letrozole |
600 mg PO once daily days 1-21 2.5 mg PO once daily days 1-28 |
Repeat cycle every 28 days |
Paclitaxel [160] |
90 mg/m² day 1, 8, and 15 |
Repeat cycle every 28 days |
Abemaciclib Fulvestrant [153] |
150 mg PO BID 500 mg IM on Days 1, 15 and 29 and once monthly thereafter |
Repeat cycle every 28 days |
Ribociclib [161] Fulvestrant |
600 mg PO once daily days 1-21 500 mg IM on Days 1, 15 and 29 and once monthly thereafter |
Repeat cycle every 28 days |
HER2-positive metastatic breast cancer regimens |
||
Trastuzumab Paclitaxel |
4 mg/kg loading dose then 2 mg/kg weekly 80 mg/m² IV weekly |
|
Trastuzumab Docetaxel |
8 mg/kg loading dose then 6 mg/kg day 1 100 mg/m² IV day 1 |
Repeat cycle every 21 days |
Pertuzumab/trastuzumab/hyaluronidase Docetaxel |
Loading dose of 1,200 mg pertuzumab/600 mg trastuzumab SC x 1 dose followed by 600 mg pertuzumab/600 mg trastuzumab SC Docetaxel is 75 mg/m2 IV, may escalate to 100 mg/m2 |
Repeat cycle every 3 week; continue until disease recurrence or unmanageable toxicity, whichever occurs first |
Trastuzumab Vinorelbine |
4 mg/kg loading dose then 2 mg/kg weekly 25 mg/m² day 1 weekly |
|
Trastuzumab Capecitabine Tucatinib [156] |
8 mg/kg loading dose then 6 mg/kg weekly 1000 mg/m2 PO BID days 1-14 300 mg PO BID |
Repeat cycle every 21 days |
Lapatinib Capecitabine |
1250 mg PO daily 2000 mg/m² daily days 1-14 |
Repeat cycle every 21 days |
Paclitaxel Lapatinib |
175 mg/m2 1500 mg/d |
Repeat cycle every 3 weeks |
AUC = area under the curve (systemic exposure) References for chemotherapy regimens: XT, [162] XP, [163] XN, [163] HER2-positive metastatic breast cancer regimens [164, 165, 166, 167] |
||
|
NCCN |
ASCO |
History and physical examination |
Year 1, every 3-4 mo Year 2, every 4 mo Year 3-5, every 6 mo Year 6+, annually |
Year 1-3, every 3-6 mo Year 4-5, every 6-12 mo Year 6+, annually |
Breast self-examination |
No recommendation |
Counseled to perform monthly breast self-examination |
Mammography |
6 mo after post-BCS radiation therapy Annually thereafter |
6 mo after definitive radiation therapy Every 6-12 mo for surveillance of abnormalities Annually if stability of abnormalities is achieved |
Pelvic examination |
Annually, for women on tamoxifen Annual exam if uterus present |
Regular gynecologic follow-up Patients on tamoxifen should be advised to report any vaginal bleeding |
Routine blood tests |
Not recommended |
Not recommended |
Imaging studies |
Not recommended |
Not recommended |
Tumor marker testing |
Not recommended |
Not recommended |
Women aged ≥65 years |
Woman aged 60-64 years with ≥1 of the following: 1. Family history of osteoporosis 2. Low body weight 3. Prior nontraumatic fracture 4. Other risk factors (eg, smoking, sedentary lifestyle) |
Postmenopausal women on aromatase inhibitors |
Premenopausal women who develop treatment related premature menopause |
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- Overview
- Presentation
- DDx
- Workup
- Treatment
- Approach Considerations
- Treatment of Invasive Breast Cancer
- Systemic Adjuvant Therapy for Breast Cancer
- Treatment of Carcinoma in Situ
- Treatment of Locally Advanced and Inflammatory Breast Cancer
- Systemic Treatment of Metastatic Breast Cancer
- Surgical Treatment of Metastatic Breast Cancer
- Pharmacologic Reduction of Breast Cancer Risk
- Prophylactic Mastectomy
- Long-Term Monitoring
- Integrative Therapy
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- Guidelines
- Medication
- Medication Summary
- Antineoplastics, Alkylating
- Antineoplastics, Anthracycline
- Calcium Metabolism Modifiers
- Antineoplastics, Antimetabolite
- Antineoplastics, Vinca Alkaloid
- Monoclonal Antibodies
- Tyrosine Kinase Inhibitors
- Antineoplastics, Antimicrotubular
- Aromatase Inhibitors
- CDK Inhibitors
- Antineoplastics, PARP Inhibitors
- Antineoplastics, Estrogen Receptor Antagonist
- PD-1/PD-L1 Inhibitors
- PI3K Inhibitors
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