Several classes of agents at the forefront of the breast cancer treatment paradigm are associated with skin toxicities that may be managed with dermatologic intervention.1 Immune checkpoint inhibitors (ICIs) may be combined with chemotherapy for the treatment of patients with triple-negative breast cancer. The chemotherapy element of these regimens is associated with dermatologic AEs including alopecia, hand-foot syndrome, nail changes, and hyperpigmentation. Furthermore, patients who receive ICIs may experience cutaneous immune-related AEs like maculopapular, eczematous, psoriasiform, lichenoid, and bullous eruptions, as well as pruritus.
Regarding targeted therapies, many HER2-directed agents are associated with acneiform rash. CDK4/6 inhibitors may cause pruritus, xerosis, and alopecia, particularly when combined with endocrine therapy. PI3K inhibitors may be associated with maculopapular or eczematous rashes, as well as periorbital edema. Additionally, maculopapular rash has been commonly reported with the use of AKT inhibition.
Clinical trials with antibosy-drug conjugates (ADCs) have shown this class of agents to be associated with maculopapular, bullous, acneiform, and lichenoid rashes, most of which are lower grade. Alopecia, stomatitis, pruritus, and hyperpigmentaiton have also been reported.
Overall, lower-grade rashes are typically managed with topical corticosteroids and oral antihistamines, whereas higher-grade rashes may require ICI interruption and treatment with systemic corticosteroids. Steroid-sparing immunomodulatory agents may also be used. Lower-grade maculopapular and eczematous rashes are often addressed with potent topical corticosteroids and systemic antihistamines, whereas higher grades of these AEs may be managed with therapy interruption and systemic corticosteroids. ADC-induced stomatitis prophylaxis may include gentle oral care, corticosteroid-containing mouthwash, and cryotherapy.
“It’s important for members of the oncology team to recognize the different morphologies of these rashes, because that is what guides dermatology-directed treatment,” Leventhal said in an interview with OncLive®.
In the interview, Leventhal discussed the prevalence of dermatologic AEs in patients receiving breast cancer treatment, highlighted the role of dermatologists in cancer survivorship, and stressed the need for oncologists to collaborate closely with dermatologists for expedited care.
Leventhal is an associate professor term at the Yale School of Medicine, as well as director of the Dermatology Residency Program and director of the Onco-Dermatology Clinic at the Yale Cancer Center Smilow Cancer Hospital in New Haven, Connecticut.
OncLive: What dermatologic AEs are most commonly associated with breast cancer treatments?
Leventhal: Dermatologic AEs are among the most common that patients with breast cancer experience. These can occur from all types of treatment for breast cancer, especially the emerging treatments, such as ICIs, targeted therapies, and ADCs. In general, most of these patients can continue to receive their life-saving cancer treatments.
This requires multidisciplinary dermatologic care. Most rashes that are mild respond well to topical remedies, [such as] topical steroids and antihistamines. Rashes that are more severe often require a drug holiday and systemic treatments as well, including prednisone or steroid-sparing drugs.
What characteristics of dermatologic AEs should clinicians look out for?
In general, most of the rashes are mild. Usually, pruritus rashes depend on the type of cancer treatment the patient is receiving. The key red-flag signs and symptoms that should prompt dermatologic intervention are painful skin, mucosal involvement, skin blisters, desquamation, and facial swelling. Other red flag signs and symptoms [include] fevers, feeling unwell, and other systemic abnormalities like transaminitis. Those should prompt immediate dermatologic intervention.
What is your advice for patients about recognizing these AEs and advocating for themselves?
It’s important that patients should fully understand the scope of dermatologic complications that can happen. At the earliest sign of a rash, they’ll know what they can do. Some [treatments] can prevent some of these toxicities. For instance, for hair loss from certain chemotherapy [and other] treatments, you can do cryotherapy—or scalp cooling—to preserve the hair. [Similarly, cryotherapy can help] reduce the severity of neuropathy and hand-foot syndrome, which is part of the spectrum called toxic erythema of chemotherapy.
Cryotherapy can also reduce the severity of nail changes. For patients who are receiving targeted therapy, sun protection, such as the use of sunscreen, is important. Patients should know that toxicities can happen to their skin, hair, and nails, so at the earliest signs, they should [address these toxicities with] their oncology team.
What is the importance of a multidisciplinary approach to dermatologic AE management in patients with cancer?
The cancer team is large, which is great. Patients have a lot of access to their advanced practice providers and oncologists. However, they don’t always see a dermatologist regularly.
I would say to the members of the oncology team: find a dermatologist you can work closely with, because having access to prompt dermatologic care is key. Sometimes there are long waits to see a dermatologist in the community. It can take weeks or months, and a lot of these dermatologic issues require immediate interaction.
I’m fortunate to work at Yale Cancer Center, where I feel like I’m thought of as an integral member of the multidisciplinary oncology team, which is great. [I have] speed dials for my oncology friends and [my patients’] advanced practice providers. However, that’s not always the case in the community. My advice to oncologists who work in the community is to find dermatology allies you can turn to when you need an expedited referral.
What might the future hold regarding dermatologic management for patients with breast cancer?
The field of oncodermatology spans all major types of cancer, in addition to survivorship. A lot of my patients now who I see in my clinic at Yale Cancer Center are cancer survivors who have sequelae that persist, such as hyperpigmentation of their skin or hair loss. Alopecia that persists after chemotherapy is another major area I help patients deal with.
Survivorship is now becoming more of a large portion of my clinic, which is great because we have wonderful treatments that many patients will continue to receive for maintenance for years to come. However, a lot of the dermatologic AEs can persist as well. It’s great that so many cancer centers across the country have dermatologists as part of the oncology team, and it’s been inspiring to see the field grow. A lot of my medical students and residents who I am mentoring are taking an interest in the field, and it’s only going to continue to grow over time.
Reference
LeVee A, Deutsh A, Lindgren ES, et al. New drugs, new toxicities: side effects of new and emerging breast cancer therapies. Am Soc Clin Oncol Educ Book. 2025;45(3):e473384. doi:10.1200/EDBK-25-473384