Breast Cancer: Pharmacologic Management

Breast cancer is the most common nondermal cancer in women, but it can also occur in men. The Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute estimates that there will be 297,790 new cases of invasive breast cancer and 55,720 new cases of ductal carcinoma in situ (DCIS) diagnosed in 2023, which will account for 15.2% of all new cancer cases in the United States.^1,2 With the widespread use of breast cancer screenings with mammograms beginning at age 50, as recommended by the US Preventive Services Task Force (USPSTF), women are increasingly diagnosed and treated in the early stages of the disease.³ 

Optimal pharmacologic treatment of breast cancer is determined based on the tumor grade, stage, hormone receptor status, mutational status and burden, and histologic subtype.

Breast Cancer Staging

The American Joint Committee on Cancer (AJCC) has developed a cancer staging system that takes several factors into account when evaluating breast cancer cases.² These factors include:

• Tumor size
• Lymph node infiltration
• Tumor grade
• Hormone receptor status
• Presence of human epidermal growth factor receptor 2 (HER2/neu)
• Menopausal status 
• The patient’s overall health

Histologic Subtype

According to the National Cancer Institute (NCI), breast cancer is categorized into 5 main subtypes, with each defined by histologic findings.² Ductal and lobular carcinomas are the most common types of breast cancer, followed by Paget disease affecting the nipple. The National Comprehensive Cancer Network (NCCN) has established treatment recommendations based on breast cancer staging and histologic subtype.⁴ 

Hormone Receptor Status

Breast cancer cells may have mutations in the estrogen receptor (ER) or the progesterone receptor (PR). They may also express abnormally high levels HER2. Immunohistochemistry is used to measure ER, PR, and HER2 expression in cancer cells.²

HER2 expression may also be measured using in situ hybridization, which is a technique that measures gene copy numbers. Biomarker testing should be performed to confirm the presence or absence of hormone receptor mutations. The results of this testing will guide treatment decisions and pharmacotherapy options.² 

Triple-negative breast cancer (TNBC), which is diagnosed when a patient has no targetable hormone receptor mutations, is associated with poorer disease outcomes and survival, and it is often more difficult to treat.⁵ 

BRCA1/2 Mutations

Studies estimate that between 5% and 10% of women with breast cancer have a germline mutation in the BRCA1 or BRCA2 genes.² The lifetime risk of developing breast cancer when harboring these mutations is 40% to 85%.² Women with breast cancer and these mutations may be treated with targeted therapies if their disease progresses. 

Pharmacotherapy for Breast Cancer

Chemotherapy

Chemotherapy uses a variety of cytotoxic drugs that interfere with cell division and growth. These agents target rapidly dividing cells by interfering with DNA synthesis through several mechanisms.⁶ Chemotherapy is typically used as a preoperative treatment and as adjuvant therapy following surgery to eliminate any remaining cancer cells. 

Types of chemotherapy agents used to treat breast cancer include:

• Alkylating agents: Create crosslinks within DNA to inhibit transcription and DNA repair processes; examples include cyclophosphamide and carboplatin⁷
• Antimetabolites: Replace bases during DNA synthesis in various stages of the cell cycle; one example is capecitabine⁸
• Antineoplastic antibiotics: Antibiotics that interfere with cell division and DNA synthesis; one example is doxorubicin⁹
• Mitotic inhibitors: Drugs that inhibit mitosis by disrupting the mitotic spindle or microtubules; examples include docetaxel and paclitaxel¹⁰

Table 1. Management Guidelines for Preferred Chemotherapy Regimens for Breast Cancer

Drug name/ Combination name	Dosage	Recommended Use	Treatment Duration
Capecitabine	1000-1250 mg/m2 twice daily	Preoperative and adjuvant therapy for high-risk TNBC	21-d cycle for 6-8 cycles: Taken on days 1-14
Dose-dense doxorubicin and cyclophosphamide (AC) followed by paclitaxel	Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, followed by paclitaxel 175 mg/m2	Preoperative and adjuvant therapy for HER2-negative breast cancer	14-d cycle for 4 cycles: Doxorubicin and cyclophosphamide IV infusion on day 1 14-d cycle for 4 cycles: Followed by paclitaxel 3h IV infusion on day 1
Dose-dense doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel	Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, followed by paclitaxel 80 mg/m2	Preoperative and adjuvant therapy for HER2-negative breast cancer	14-d cycle for 4 cycles: Doxorubicin and cyclophosphamide IV infusion on day 1 Weekly infusion for 12 wk: Followed by paclitaxel 1h IV infusion
Pembrolizumab + chemotherapy followed by adjuvant pembrolizumab	Preoperative: Pembrolizumab 200 mg, paclitaxel 80 mg/m2, and carboplatin AUC 5 Followed by: Pembrolizumab 200 mg, doxorubicin 80 mg/m2 (or epirubicin 90 mg/m2 ), and cyclophosphamide 600 mg/m2  Followed by: Pembrolizumab 200 mg as adjuvant therapy	Preoperative and adjuvant therapy for HER2-negative breast cancer	Preoperative, 21-d cycle for 4 cycles: Pembrolizumab IV infusion on day 1; paclitaxel IV infusion on days 1, 8, and 15; and IV carboplatin on day 1 Followed by 21-d cycle for 4 cycles: Pembrolizumab IV infusion on day 1, doxorubicin/epirubicin IV infusion on day 1, and cyclophosphamide IV infusion on day 1 Followed by 21-d cycle for 9 cycles: Pembrolizumab IV infusion on day 1
Docetaxel and cyclophosphamide (TC)	Docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2	Preoperative and adjuvant therapy for HER2-negative breast cancer	21-d cycle for 4-6 cycles: Docetaxel and cyclophosphamide IV infusion on day 1
Docetaxel, carboplatin, and trastuzumab (TCH)	Docetaxel 75 mg/m2 and carboplatin AUC 6 Dosing of trastuzumab varies	Preoperative and adjuvant therapy for HER2-positive breast cancer	21-d cycle for 6 cycles: Docetaxel and carboplatin IV infusion on day 1 with trastuzumab 4 mg/kg for 1 wk Followed by: Trastuzumab 2 mg/kg IV infusion for 17 wk Followed by: Trastuzumab 6 mg/kg IV infusion on a 21-d cycle to complete 1 y of treatment
TCH + pertuzumab	Docetaxel 75 mg/m2 and carboplatin AUC 6  Dosing of trastuzumab and pertuzumab varies	Preoperative and adjuvant therapy for HER2-positive breast cancer	21-d cycle for 6 cycles: Docetaxel and carboplatin with trastuzumab 8 mg/kg and pertuzumab 840 mg IV infusion on day 1 Followed by: Trastuzumab 6 mg/kg and pertuzumab 420 mg IV infusion on day 1 of 21-d cycle to complete 1 y of treatment
Trastuzumab + paclitaxel	Paclitaxel 80 mg/m2 with trastuzumab 4 mg/kg	Preoperative and adjuvant therapy for HER2-positive breast cancer	Paclitaxel IV infusion weekly for 12 wk; trastuzumab IV infusion with first dose of paclitaxel After 12 weeks: trastuzumab 2 mg/kg weekly to complete 1 y of treatment; may also prescribe trastuzumab 6 mg/kg every 21 d to complete 1 y of treatment

AUC = area under the curve; HER2 = human epidermal growth factor-2; IV = intravenous; TNBC = triple-negative breast cancer.

From the NCCN Breast Cancer Treatment Guidelines.⁴

Endocrine Therapy

For patients with HR-positive breast cancer, endocrine therapy with aromatase inhibitors and estrogen modulators is the preferred treatment.⁵ These medications may be used as single agents or in combination with chemotherapy. Ovarian suppression or ablation may be used to prevent the ovaries from making estrogen. Patients may undergo oophorectomy or receive treatment with luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists. 

Table 2. Management Guidelines for Endocrine Therapy for Breast Cancer

Drug	Dose	Administration	Recommended Use	Duration of Treatment
Anastrozole	1 mg daily	Tablet taken orally with or without food	Adjuvant treatment in postmenopausal women with HR-positive stages I and II breast cancer	Optimal treatment duration is unknown; studies show up to 5 y of use
Exemestane	25 mg daily	Tablet taken orally after eating	Adjuvant treatment in postmenopausal women with ER-positive stages I and II breast cancer	Treat until 5 y of endocrine therapy is complete
Letrozole	2.5 mg daily	Tablet taken orally with or without food	Adjuvant treatment for postmenopausal women with HR-positive stages I and II breast cancer Extended adjuvant treatment for postmenopausal women with early breast cancer after receiving tamoxifen treatment for 5 y	Optimal treatment duration is unknown; studies show up to 5 y of use; discontinue treatment if cancer relapses
Tamoxifen	20-40 mg daily	Oral solution; doses greater than 20 mg should be given twice daily	Adjuvant treatment for ER-positive stage I or II breast cancer Adjuvant treatment for DCIS to reduce the risk of invasive breast cancer	As adjuvant treatment: Treat for 5-10 y DCIS: Treat for 5 y

DCIS = ductal carcinoma in situ; ER = estrogen receptor; HR =  hormone receptor; 

From FDA-approved prescribing information.^11-14

From NCCN Breast Cancer Treatment Guidelines.⁴

Immunotherapy

Pembrolizumab is an immunotherapy agent that binds to and blocks the programmed death-1 (PD-1) receptor, preventing it from interacting with programmed death ligand-1 (PD-L1) found on the surface of tumor cells.¹⁵ This is known as immune checkpoint blockade, and it sensitizes a patient’s T cells to their cancer. 

Table 3. Management Guidelines for Immunotherapy for Breast Cancer

Drug	Dosage	Administration	Recommended Use	Treatment Duration
Pembrolizumab	200 mg every 3 wk or 400 mg every 6 wk	IV infusion over 30 min	As neoadjuvant treatment for high-risk stage I or II or TNBC	In combination with chemotherapy: Treat for 24 wk or until unacceptable toxicity or disease progresses Single agent: Treat for ≤7 wk or until unacceptable toxicity or disease progresses

TNBC = triple-negative breast cancer. 

From FDA-approved prescribing information.¹⁶

From NCCN Breast Cancer Treatment Guidelines.⁴

Targeted Therapies

Several targeted therapies are available for treating early-stage breast cancer. Many of these agents target HER2 overexpression in breast cancer cells. Others target germline mutations in BRCA1/2 or cyclin-dependent kinases 4 and 6 (CDK4/6) to induce cell cycle arrest. Targeted therapies may be used alone or in combination with chemotherapy or endocrine therapy as adjuvant treatments.⁴ 

Table 4. Management Guidelines for Targeted Therapies for Breast Cancer

Drug	Dosage	Administration	Recommended Use	Treatment Duration
Abemaciclib	150 mg twice daily  when combined with an aromatase inhibitor or tamoxifen	Tablet taken orally with or without food	Used in combination with endocrine therapy for adjuvant treatment of HR-positive, HER2-negative, node-positive early breast cancer with a high risk of recurrence	Take for 2 y or until unacceptable toxicity or disease progresses
Ado-trastuzumab emtansine	3.6 mg/kg	IV infusion over 90 min every 3 weeks on a 21-d cycle	Adjuvant treatment for HER2-positive stages I and II breast cancer with residual disease	Administer for a total of 14 cycles or until unacceptable toxicity occurs or disease progresses
Neratinib	240 mg once daily	6 tablets taken orally with food	Extended adjuvant treatment for early-stage, HER2-positive breast cancer	Take daily for 1 y or until disease recurs
Olaparib	300 mg twice daily	2 tablets taken orally with or without food	Used as an adjuvant treatment for patients with HER2-negative, high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy	Take on day 1 of 28-d cycle for 1 y
Pertuzumab	Initial dose of 840 mg; subsequent doses of 420 mg	IV infusion over 60 min	HER2-positive stage I or II, inflammatory breast cancer; adjuvant treatment of stage I or II HER2-positive disease with a high risk of recurrence	Administer for 3-6 cycles for early breast cancer in combination with chemotherapy or trastuzumab
Pertuzumab, trastuzumab and hyaluronidase-zzxf	Initial dose: pertuzumab 1200 mg, trastuzumab 600 mg, and hyaluronidase 30,000 units in a 15-mL injection Maintenance dose: pertuzumab 600 mg, trastuzumab 600 mg, and hyaluronidase  20,000 units in a 10-mL injection	SC injection into the thigh over 5 min every 3 weeks; do not administer intravenously	May be substituted in treatment regimens where IV pertuzumab and trastuzumab are used	Early breast cancer: Administer for 3-6 cycles Adjuvant treatment: Continue to treat for 1 y (18 cycles maximum) until unacceptable toxicity occurs or disease recurs (whichever comes first)
Trastuzumab	In combination with chemotherapy: Initial dose of 4 mg/kg weekly with chemotherapy; subsequent doses at 2 mg/kg every 3 wk Single agent: Initial dose of 8 mg/kg; subsequent doses at 6 mg/kg every 3 wk	First dose: IV infusion over 90 min Subsequent doses: IV infusion over 30-90 min, depending on patient’s tolerance	Used for adjuvant treatment of HER2-overexpressing, node-positive or node-negative (ER/PR-negative or with 1 high-risk feature) breast cancer	Treat for 1 y in combination with chemotherapy or as a single agent after chemotherapy
Trastuzumab/hyaluronidase	Trastuzumab 600 mg with hyaluronidase  10,000 units	SC injection over 2-5 min	May be substituted for any treatment regimen using IV trastuzumab	Treat for 1 y or until disease recurs; it is not recommended to treat for more than 1 y

ER = estrogen receptor; HER2 = human epidermal growth factor receptor-2; HR = hormone receptor; IV = intravenous; PR = progesterone receptor; SC = subcutaneous.

From FDA-approved prescribing information.^17-24

From NCCN Breast Cancer Treatment Guidelines.⁴

Pharmacotherapy Recommendations for Breast Cancer

The NCCN has recently updated their guidelines regarding breast cancer treatment and management.⁴ Herein are outlined the pharmacologic guidelines for treating DCIS and early-stage invasive breast cancer. A separate article will detail treatments for locally advanced, recurrent, or stage IV breast cancer. 

Ductal Carcinoma In Situ

The main goal of treatment for DCIS is to prevent a patient’s cancer from progressing to invasive disease. Patients are first treated with surgery (either breast-conserving surgery or total mastectomy) and/or radiation therapy. For those with HR-positive cancer, adjuvant endocrine therapy is key to reducing the risk of recurrence. 

Tamoxifen is the preferred endocrine therapy following surgery and/or radiation therapy. Premenopausal and postmenopausal patients with ER-positive breast cancer are ideal candidates for treatment with tamoxifen. The standard dosage is 20 mg/d for up to 5 years. Patients who cannot tolerate the standard dose are given low-dose tamoxifen at 5 mg/d for up to 3 years. 

Postmenopausal women, particularly those younger than 60 years, are preferentially treated with an aromatase inhibitor such as anastrozole. Those who are at increased risk for thromboembolism are also candidates for treatment with an aromatase inhibitor. 

Early-Stage Invasive Breast Cancer

As with management of DCIS, early-stage invasive breast cancer is first treated with surgery and/or radiation therapy, when possible. Breast-conserving surgery or a total mastectomy is followed by adjuvant systemic therapy to eliminate any remaining cancer cells. 

Additional testing to stage and grade the tumor and identify biomarkers and hormone receptor status will further guide treatment decisions. Patients with TNBC or operable early-stage, HER-2 positive breast cancer may receive systemic therapy first to shrink the tumor prior to surgery. The NCCN recommends several chemotherapy regimens, endocrine therapies, and HER2 therapies to treat early-stage invasive breast cancer. 

Preoperative Therapies

Patients who are eligible for preoperative therapy include those with:

• Inoperable or locally advanced disease (including patients with inflammatory breast cancer)
• Advanced nodal disease
• T4 tumors 
• Operable breast cancer who want to undergo breast-conserving surgery but whose tumor is too large 
• Cancer that is likely to respond to treatment

Preoperative therapy is not recommended for patients with extensive in situ disease that may be invasive in nature, those with poorly delineated tumors, and those whose tumors are not palpable or cannot be assessed. 

Adjuvant Endocrine Therapy

Systemic adjuvant therapy following surgery is preferred in early-stage disease to reduce the risk of recurrence. The NCCN recommends adjuvant endocrine therapy for all patients with ER-positive or PR-positive disease, regardless of their age, lymph node status, and other adjuvant therapies. 

Postmenopausal patients are recommended to receive:

• An aromatase inhibitor for 5 years as initial adjuvant treatment
• Tamoxifen for 2 to 3 years followed by an aromatase inhibitor to complete 5 total treatment years
• Tamoxifen for 4.5 to 6 years followed by an aromatase inhibitor for 5 years
• Tamoxifen for 10 years total 

Premenopausal patients are recommended to receive:

• Tamoxifen for 5 years with or without ovarian suppression
• An aromatase inhibitor for 5 years plus ovarian suppression 

The NCCN guidelines state there is no discernible difference between the aromatase inhibitors anastrozole, letrozole, or exemestane. 

Adjuvant Chemotherapy

The NCCN provides several chemotherapy regimen recommendations based on the findings of phase 3 clinical trials. The preferred treatment regimens include:

• Dose-dense doxorubicin and cyclophosphamide (AC) with dose-dense sequential paclitaxel
• Dose-dense AC followed by sequential paclitaxel administered weekly
• Docetaxel plus cyclophosphamide (TC)

HER2-Targeted Therapy

Patients with HER2-positive breast cancer are recommended to receive targeted therapy. Trastuzumab has been extensively studied as an adjuvant therapy. The NCCN recommends the combination of chemotherapy and trastuzumab to treat patients with HER2-positive tumors greater than 1 cm across and for patients with small (0.6 to 1.0 cm) tumors and node-negative disease. Ado-trastuzumab emtansine may be substituted in cases where IV trastuzumab would be used. 

Preferred treatment combinations include:

• Paclitaxel followed by trastuzumab for 1 year, with treatment beginning at the first paclitaxel dose 
• Docetaxel or paclitaxel, carboplatin, and trastuzumab (TCH) regimen
• TCH plus pertuzumab (if the patient did not previously receive pertuzumab as a neoadjuvant treatment)

Patients with residual disease following preoperative treatment may receive ado-trastuzumab alone for 14 cycles. If treatment is not tolerated and is discontinued due to toxicity, treatment with trastuzumab with or without pertuzumab is recommended.

Patients with a high risk of recurrence and HR-positive, HER2-positive disease should be considered for extended adjuvant neratinib therapy after completing a trastuzumab regimen. 

HER2-Negative and TNBC Treatments

Patients with HER2-negative breast cancer or with high-risk TNBC cannot be treated with trastuzumab. Instead, the NCCN recommends preoperative/adjuvant treatment with dose-dense AC, TC, or olaparib (for patients with germline BRCA1/2 mutations). 

Patients with high-risk TNBC are recommended to receive preoperative treatment with:

1. Carboplatin, paclitaxel, and pembrolizumab followed by
2. Preoperative cyclophosphamide, doxorubicin (or epirubicin), and pembrolizumab followed by 
3. Adjuvant pembrolizumab 

Patients with TNBC and residual disease following preoperative therapy may also be treated with capecitabine. 

Patients with early-stage, HR-positive but HER2-negative disease may be eligible to receive 2 years of adjuvant abemaciclib therapy in combination with endocrine therapy. HR-positive, HER2-negative patients with germline BRCA1/2 mutations may also be eligible to receive 1 year of adjuvant olaparib treatment following the completion of adjuvant chemotherapy. 

Monitoring Side Effects, Adverse Events, and Drug-Drug Interactions During Breast Cancer Treatment

Monitoring of a patient’s health and adverse events during treatment is imperative. Many pharmacologic treatments for cancer — particularly chemotherapies — exhibit off-target effects that increase toxicity. Endocrine therapies also interfere with bone health and mineral density, increasing the risk of osteoporosis and fractures. The NCCN treatment guidelines recommend the use of bisphosphonate to reduce the risk of bone fractures and maintain or increase bone mineral density.⁴ There currently are no recommendations for the length of bisphosphonate treatment. 

The chart below details common adverse events, drug-drug interactions, and special populations to take into consideration when treating patients with breast cancer. Geriatric patients and those with renal or hepatic insufficiency or impairment should be treated with caution in most cases.

Table 5. Side Effect Profiles for Chemotherapy for Breast Cancer 

Drug	Most Common Adverse Events	Drug-Drug Interactions	Special Population Considerations
Capecitabine	GI symptoms (nausea, vomiting, diarrhea, constipation), abdominal pain, dyspepsia, skin rash, alopecia, pyrexia, headache, dizziness, fatigue, dysgeusia, infections, anorexia, epistaxis, neutropenia Warnings: Severe diarrhea, coagulopathy, DPD deficiency, cardiotoxicity, severe skin reactions, dehydration and renal failure, low blood cell counts, hyperbilirubinemia	Anticoagulants, leucovorin, CYP2C9 substrates, phenytoin, allopurinol	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients and those with renal or hepatic insufficiency
Carboplatin	GI symptoms, abdominal pain, decreased appetite, fever, rash, upper respiratory tract infection, cough, musculoskeletal pain, headache, back pain, joint pain, fatigue and weakness Warnings: Infusion reaction	None indicated	Do not use in pregnant or breastfeeding patients
Cyclophosphamide	Nausea, vomiting, abdominal pain, diarrhea, anorexia, low blood cell counts, alopecia, skin rash Warnings: Immunosuppression, myelosuppression, cardiotoxicity, renal and urinary tract toxicity, veno-occlusive liver disease, impaired wound healing, hyponatremia, infertility, secondary malignancies, pulmonary toxicity	ACE inhibitors, paclitaxel, protease inhibitors, natalizumab, thiazide diuretics, anthracyclines, trastuzumab, pentostatin, cytarabine, amiodarone, G-CSF, GM-CSF, indomethacin, amphotericin, azathioprine, etanercept, busulfan, tamoxifen, metronidazole, coumarins, cyclosporine	Use with caution in geriatric patients and those with severe renal or hepatic impairment
Docetaxel	GI symptoms, infections, low blood cell count, neuropathy, dyspnea, dysgeusia, nail disorders, alopecia, myalgia, skin reactions, anorexia Warnings: Hepatic impairment, hypersensitivity, skin and neurologic reactions, colitis, toxic deaths, eye disorders	CYP3A4 inhibitors or inducers	Do not use in pregnant or breastfeeding patients; patients with severe hepatic impairment should not be treated with docetaxel
Doxorubicin	Alopecia, nausea, vomiting, urticaria, pyrexia, chills, asthenia Warnings: Cardiotoxicity, injection site reaction, hepatotoxicity, secondary leukemia, immunosuppression and increased risk of infection	CYP3A4, CYP2D6, and P-gp inhibitors or inducers; concomitant use of 6-mercaptopurine, dexrazoxane, or trastuzumab	Do not use in pregnant or breastfeeding patients; reduce dose in patients with severe hepatic impairment
Epirubicin	GI symptoms, low blood cell counts, hot flashes, amenorrhea, pyrexia, infection, alopecia, skin rash and pruritus Warnings: Cardiotoxicity, secondary leukemia, tumor lysis syndrome, hematologic toxicity	Cardiotoxic agents, paclitaxel, docetaxel, cimetidine	Do not use in pregnant or breastfeeding patients; reduce dose in patients with renal or hepatic impairment
Paclitaxel	Low blood cell count, infections, myalgia, arthralgia, nausea, vomiting, diarrhea, elevated liver enzyme levels Warnings: Bradycardia, hypotension, hypersensitivity	CYP2C8 and CPY3A4 inhibitors and inducers	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients

ACE = angiotensin-converting enzyme; DPD = dihydropyrimidine dehydrogenase; G-CSF = granulocyte colony-stimulating factor; GI = gastrointestinal; GM-CSF = granulocyte-macrophage colony-stimulating factor; P-gp = P-glycoprotein.

From FDA-approved prescribing information.^25-31

Table 6. Side Effect Profiles for Endocrine Therapies for Breast Cancer

Drug	Most Common Adverse Events	Drug-Drug Interactions	Special Population Considerations
Anastrozole	Bone pain, fractures, arthralgia, headache, cough, dyspnea, hot flashes, lymphedema, insomnia, nausea, vomiting Warnings: Osteoporosis, elevated cholesterol levels, ischemic cardiovascular events	Estrogen-containing treatments, tamoxifen, warfarin, other drugs that inhibitor CYP450	Do not use in pregnant or breastfeeding patients
Exemestane	Hot flashes, arthralgia, fatigue, sweating, insomnia, headache Warnings: Osteoporosis	CYP3A4 inducers	Do not use in pregnant or breastfeeding patients; do not use in premenopausal women
Letrozole	Hot flashes, bone fractures, arthralgia, weight gain, nausea, vomiting, night sweats, edema, back pain, depression, vaginal bleeding and irritation, headache alopecia Warnings: Osteoporosis, elevated cholesterol levels, fatigue and dizziness	Tamoxifen, warfarin, cimetidine	Do not use in pregnant or breastfeeding patients; adjust dose in patients with hepatic impairment; use with caution in geriatric patients
Tamoxifen	Hot flashes, nausea, weight loss, skin changes, irregular menses, vaginal discharge, fluid retention Warnings: Increased risk of uterine sarcoma, endometrial cancer, and liver cancer; venous thrombosis; low blood cell counts; eye complications	Concomitant use with letrozole is not recommended, strong inhibitors and inducers of CYP3A4, strong inhibitors of CYP2D6, warfarin	Do not use in pregnant or breastfeeding patients

From FDA-approved prescribing information^11-14

Table 7. Side Effect Profile for Pembrolizumab for Breast Cancer

Drug	Most Common Adverse Events	Drug-Drug Interactions	Special Population Considerations
Pembrolizumab	GI symptoms (nausea, vomiting, diarrhea, constipation), pyrexia, fatigue, stomatitis, abdominal pain, skin rash, alopecia, myalgia, arthralgia, cough, decreased appetite, headache, peripheral neuropathy, insomnia Warnings: Severe immune-related reactions, infusion reactions	None indicated	Do not use in pregnant or breastfeeding patients

GI = gastrointestinal.

From FDA-approved prescribing information¹⁶

Table 7. Side Effect Profiles for Targeted Therapies for Breast Cancer

Drug	Most Common Adverse Events	Drug-Drug Interactions	Special Population Considerations
Abemaciclib	GI symptoms (nausea, vomiting, diarrhea, constipation), low blood cell count, fatigue, decreased appetite, headache, infections, abdominal pain, alopecia Warnings: Neutropenia, severe diarrhea, venous thrombosis, hepatotoxicity, ILD	Moderate or strong CYP3A inhibitors and inducers	Do not use in pregnant or breastfeeding patients
Ado-trastuzumab emtansine	Nausea, headache, musculoskeletal pain, fatigue, constipation, epistaxis, elevated transaminase levels Warnings: Pulmonary toxicity, infusion reaction and hypersensitivity, left ventricular dysfunction, thrombocytopenia, neurotoxicity, hemorrhage	Strong CYP3A4 inhibitors	Do not use in pregnant or breastfeeding patients; use with caution in patients with severe renal and hepatic impairment
Neratinib	GI symptoms, fatigue, abdominal pain, decreased appetite, stomatitis, dyspepsia, skin rash, muscle spasms, infections, weight loss, elevated liver enzyme levels Warnings: Severe diarrhea, hepatotoxicity	Avoid PPIs while taking neratinib; moderate or strong CYP3A4 inhibitors and inducers; P-gp inhibitors	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients
Olaparib	Low blood cell counts, nausea, vomiting, fatigue Warning: Risk of developing MDS/AML, venous thrombosis, pneumonitis	Other myelosuppressive agents; moderate or strong CYP3A inhibitors and inducers	Do not use in pregnant or breastfeeding patients
Pertuzumab, trastuzumab, and hyaluronidase-zzxf	GI symptoms, skin reactions, nail complications, alopecia, stomatitis, hemorrhoids, abdominal pain, low blood cell count, fatigue, asthenia, pyrexia, peripheral edema, headache, peripheral neuropathy, dysgeusia, myalgia, arthralgia, back pain, epistaxis, cough, infections, dyspnea, decreased appetite, insomnia, hot flush Warnings: Cardiomyopathy, pulmonary toxicity, neutropenia, administration-related reaction and hypersensitivity	Avoid anthracycline-based regimens for up to 7 mo after discontinuing treatment to reduce risk of cardiac dysfunction	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients to reduce risk of cardiac dysfunction
Trastuzumab	GI symptoms, pyrexia, cough, infections, dyspnea, headache, low blood cell count, myalgia, rash, fatigue Warnings: Cardiomyopathy, pulmonary toxicity, infusion reaction, neutropenia	Avoid anthracycline-based regimens for up to 7 mo after discontinuing treatment to reduce risk of cardiac dysfunction	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients to reduce risk of cardiac dysfunction
Trastuzumab/hyaluronidase	Fatigue, alopecia, asthenia, myalgia, rash, cough, pyrexia, dyspnea, peripheral sensory neuropathy, hot flush, infections, mucosal inflammation, leukopenia, nausea, diarrhea, decreased appetite Warnings: Cardiomyopathy, pulmonary toxicity, infusion reaction, neutropenia	Avoid anthracycline-based regimens for up to 7 mo after discontinuing treatment to reduce risk of cardiac dysfunction	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients to reduce risk of cardiac dysfunction
Pertuzumab	Diarrhea, nausea, vomiting, alopecia, neutropenia, peripheral neuropathy Warnings: Infusion reaction, left ventricular dysfunction, hypersensitivity	None indicated	Do not use in pregnant or breastfeeding patients

AML=acute myeloid leukemia; GI = gastrointestinal; ILD=Interstitial lung disease; MDS=myelodysplastic syndrome; P-gp = P-glycoprotein; PPI = proton pump inhibitor

From FDA-approved prescribing information^17-24

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27. Cyclophosphamide. DailyMed. Updated September 8, 2021. Accessed May 6, 2023. 
28. Docetaxel Anhydrous. DailyMed. Updated October 18, 2022. Accessed May 6, 2023. 
29. Doxorubicin Hydrochloride. DailyMed. Updated February 25, 2021. Accessed May 6, 2023. 
30. Epirubicin Hydrochloride. Updated November 28, 2007. Accessed May 6, 2023. 
31. Paclitaxel. DailyMed. Updated October 27, 2022. Accessed May 6, 2023.

Author Bio

Emily Wagner, MS, earned a Bachelor of Science in biotechnology from the Rochester Institute of Technology in 2018 and a Master of Science in biomedical sciences with a focus in pharmacology from the University of Colorado Anschutz Medical Campus in 2020. During her thesis work, she studied non-small cell lung cancer and how the immune system plays a role in response to different treatments. Emily currently lives in Colorado where she enjoys the mountains, spending time with her dog, baking, and reading a good book.