Vignette:

History of Present Illness: A 56-year-old postmenopausal woman with recently diagnosed breast cancer (human epidermal grow factor receptor 2 [HER2] positive; estrogen receptor/progesterone receptor [ER/PR] positive; nonmetastatic) presents to the hospital with shortness of breath and chest pain. Her ECG is in normal sinus rhythm, but a chest CT scan reveals acute bilateral pulmonary emboli . Cycle 2 of chemotherapy was 9 days ago.

Medical History: HER2 positive; ER/PR positive; nonmetastatic breast cancer; hypertension; hyperlipidemia; chronic obstructive pulmonary disease; anxiety

Current Medications: Lisinopril 20 mg by mouth daily, pravastatin 40 mg by mouth nightly, duloxetine 60 mg by mouth daily, fluticasone propionate and salmeterol 250 mcg/50 mcg 1 puff by mouth twice daily, albuterol HFA (hydrofluoroalkane) 1 or 2 puffs by mouth every 6 hours as needed for shortness of breath, and clonazepam 0.5 mg by mouth twice daily as needed for anxiety. Adjuvant chemotherapy given every 14 days for four cycles total: cyclophosphamide 600 mg/m² intravenously on day 1, doxorubicin 60 mg/m² intravenously on day 1, pegfilgrastim 6 mg subcutaneously on day 2

Social History: Denies tobacco, alcohol, illicit drug use

Allergies: No known drug allergies

Vital Signs: Blood pressure 148/93 mm Hg, heart rate 144 beats/minute, respiratory rate 21 breaths/minute, temperature 98.6°F (37°C)

Laboratory Values: WBC 2.72 × 10³ cells/mm³ (SI 2.72 × 10⁹/L), Hgb 7.4 g/dL (SI 74 g/L), Plt 62,000/mm³ (SI 62 × 10⁹/L), neutrophil count 1380 cells/mm³ (SI 1.38 × 10⁹/L)

Procedure Data: ECG: normal sinus rhythm, T-wave abnormality, consider anterior ischemia. Abnormal ECG

CT Chest: Multiple bilateral acute PE extending from the distal right and left pulmonary arteries

Upper/Lower Extremity Dopplers: Positive for occlusive deep venous thrombosis (DVT) of the right popliteal vein and occlusive thrombus of the left peroneal veins. No right upper extremity DVT

Other Data: N/A

Question 1

Which current medication is likely to cause congestive heart failure (CHF)?

1. Clonazepam
2. Cyclophosphamide
3. Doxorubicin
4. Duloxetine

Answer: 3. Doxorubicin

Rationale: Doxorubicin is an anthracycline, and this class is well known to carry a risk of cardiotoxicity, especially CHF. None of the other medications cause CHF.

Citation:

Shord SS, Cordes LM. Cancer treatment and chemotherapy. In: DiPiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach, 10e. McGraw-Hill. Available at http://accesspharmacy.mhmedical.com.mwu.idm.oclc.org/content.aspx?bookid=1861§ionid=146074145.

Question 2

The patient calls the office 3 days after chemotherapy with concerns of significant pain in her hips and legs. Which medication is most likely contributing to the patient’s bone pain?

1. Duloxetine
2. Lisinopril
3. Pegfilgrastim
4. Pravastatin

Answer: 3. Pegfilgrastim

Rationale: Pegfilgrastim and other WBC growth factors cause bone pain. None of the other medications listed cause bone pain.

Citation:

Neulasta [package insert]. Amgen, 2018. Available at https://www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/neulasta/neulasta_pi_hcp_english.pdf.

Question 3

Once the patient completes the four cycles of adjuvant chemotherapy, what breast cancer medication should be added to her treatment plan?

1. Lapatinib
2. Olaparib
3. Tamoxifen
4. Trastuzumab

Answer: 4. Trastuzumab

Rationale: Because this patient has HER2-positive disease, she will need HER2-targeted therapy with trastuzumab. Lapatinib is not indicated for adjuvant HER2 treatment and is only used in the metastatic setting. Olaparib is used in patients who have a BRCA, not HER2, mutation. Tamoxifen is indicated in patients whose breast cancer is hormone positive; however, it would not be best for this patient because of its increased risk of venous thromboembolism (VTE), and the patient was recently diagnosed with a PE.

Citation:

Barnett CM, Boster B, Michaud L. Breast cancer. In: DiPiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach, 10e. McGraw-Hill. Available at http://accesspharmacy.mhmedical.com.mwu.idm.oclc.org/content.aspx?bookid=1861§ionid=146074631.

Question 4

Which endocrine therapy is best for this patient’s breast cancer?

1. Fulvestrant
2. Letrozole
3. Palbociclib
4. Tamoxifen

Answer: 2. Letrozole

Rationale: Palbociclib is not FDA approved as monotherapy and should be combined with endocrine therapy. Palbociclib is also only indicated for metastatic breast cancer, which this patient does not have. Given the risk of VTE with tamoxifen therapy and the patient’s recently diagnosed PE, tamoxifen would not be best for her hormone-positive breast cancer. Fulvestrant is hormone therapy but plays no role in adjuvant breast cancer treatment; however, fulvestrant is used in the treatment of metastatic breast cancer. Letrozole is the best and only correct answer. This patient is postmenopausal, and an aromatase inhibitor (letrozole) is indicated for at least 5 years and up to 10 years.

Citations:

1. Barnett CM, Boster B, Michaud L. Breast cancer. In: DiPiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach, 10e. McGraw-Hill. Available at http://accesspharmacy.mhmedical.com.mwu.idm.oclc.org/content.aspx?bookid=1861§ionid=146074631.

2. National Comprehensive Cancer Network (NCCN). NCCN Guidelines for Breast Cancer, version 4, 2018. Available at https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.

Question 5

What anticoagulant therapy would be most appropriate for this patient’s PE?

1. Apixaban
2. Dabigatran
3. Dalteparin
4. Warfarin

Answer: 3. Dalteparin

Rationale: Given that the patient has, and will likely continue to intermittently have, thrombocytopenia because she is actively receiving treatment, dalteparin would be the best anticoagulation for her. According to data from the CLOT trial, dalteparin is superior to warfarin in preventing VTE recurrence. Dalteparin is a category 1–recommended therapy in the NCCN guidelines. Few data support the use of dabigatran and apixaban for the treatment of VTE in patients with cancer. Some patients in the AMPLIFY study had cancer, but patients with Plt less than 100,000/mm³ were excluded.

Citations:

1. National Comprehensive Cancer Network (NCCN). NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease, version 2, 2018. Available at https://www.nccn.org/professionals/physician_gls/pdf/vte.pdf.

2. Agnelli G, Buller HR, Choen A, et al. Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial. J Thromb Haemost 2015;13:2187-91.

3. Lee AYY, Levine MN, Baker RI, et al. Low-molecular-weight-heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003;349:146-53.