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Dermatology

Worsening Rash in a Patient With Metastatic Breast Cancer

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.

1 Credit CME

JAMA Oncology

Published Online: February 16, 2023

JAMA Oncology Clinical Challenge

Article Information and Disclosures

Michael J. Pierro, MD¹;

April J. Zhang, MD²;

Lubna N. Chaudhary, MD, MS¹

Author Affiliations

¹Division of Hematology and Oncology, Department of Internal Medicine, Medical College of Wisconsin, Milwaukee
²Department of Dermatology, Medical College of Wisconsin, Milwaukee

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A 56-year-old woman presented at the clinic for follow-up of metastatic hormone receptor–positive, ERBB2-negative breast cancer. She had locally advanced disease that was invading the skin overlying her right breast and metastatic disease to the thoracic and lumbar spine, liver, and mediastinal, axillary, and retroperitoneal lymph nodes. Her disease had progressed after receiving first-line therapy with palbociclib and anastrozole. Subsequent treatments with fulvestrant and paclitaxel were also followed by progressive disease. She received treatment with capecitabine; after 6 weeks of treatment, she developed some redness on her hands and feet that resolved on its own.

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B. Inflammation of actinic keratoses

Capecitabine is an orally bioavailable prodrug of fluorouracil that was initially approved by the US Food and Drug Administration for treating breast and colorectal cancer and has since gained additional indications for various solid tumor cancers. After metabolism to active fluorouracil in the target tissue, the drug exhibits a cytotoxic effect through incorporation within the DNA, which is followed by strand breaks, inhibition of RNA synthesis, and inhibition of thymidylate synthase.¹^,2 There are several cutaneous adverse effects associated with capecitabine, such as palmar-plantar erythrodysesthesia, vitiligo, pruritus, dermatitis, alopecia, onycholysis, and the inflammation of preexisting actinic keratoses (AKs).

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Article Information

Corresponding Author: Michael Pierro, MD, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226 (mpierro@mcw.edu).

Published Online: February 16, 2023. doi:10.1001/jamaoncol.2022.6895

Conflict of Interest Disclosures: Dr Chaudhary reported personal fees from Puma Biotechnology, Seattle Genetics, Gilead Oncology, AstraZeneca, and Novartis Advisory as well as grants from Regeneron Pharmaceuticals outside the submitted work. No other disclosures were reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

References

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Higa GM , Kovach RF , Abraham J . Actinic keratosis and capecitabine therapy. J Oncol Pharm Pract. 2005;11(4):151-153. doi:10.1191/1078155205jp163cr PubMed Google Scholar Crossref

Jansen MHE , Kessels JPHM , Nelemans PJ , et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med. 2019;380(10):935-946. doi:10.1056/NEJMoa1811850 PubMed Google Scholar Crossref

Lewis KG , Lewis MD , Robinson-Bostom L , Pan TD . Inflammation of actinic keratoses during capecitabine therapy. Arch Dermatol. 2004;140(3):367-368. doi:10.1001/archderm.140.3.367 PubMed Google Scholar Crossref

Al-Niaimi F , Lyon C . Resolving actinic keratoses: an expected side-effect of capecitabine therapy. Clin Exp Dermatol. 2012;37(1):68-69. doi:10.1111/j.1365-2230.2011.04114.x PubMed Google Scholar Crossref

Peramiquel L , Dalmau J , Puig L , Roé E , Fernández-Figueras MT , Alomar A . Inflammation of actinic keratoses and acral erythrodysesthesia during capecitabine treatment. J Am Acad Dermatol. 2006;55(5)(suppl):S119-S120. doi:10.1016/j.jaad.2005.11.1100 PubMed Google Scholar Crossref

Schauder DM , Kim J , Nijhawan RI . Evaluation of the use of capecitabine for the treatment and prevention of actinic keratoses, squamous cell carcinoma, and basal cell carcinoma: a systematic review. JAMA Dermatol. 2020;156(10):1117-1124. doi:10.1001/jamadermatol.2020.2327 PubMed Google Scholar Crossref

Antoniolli LP , Escobar GF , Peruzzo J . Inflammatory actinic keratosis following capecitabine therapy. Dermatol Ther. 2020;33(6):e14082. doi:10.1111/dth.14082 PubMed Google Scholar Crossref

Ceilley RI . Mechanisms of action of topical 5-fluorouracil: review and implications for the treatment of dermatological disorders. J Dermatolog Treat. 2012;23(2):83-89. doi:10.3109/09546634.2010.507704 PubMed Google Scholar Crossref

Saif MW , Black G , Johnson M , Russo S , Diasio R . Radiation recall phenomenon secondary to capecitabine: possible role of thymidine phosphorylase. Cancer Chemother Pharmacol. 2006;58(6):771-775. doi:10.1007/s00280-006-0223-8 PubMed Google Scholar Crossref

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.