As treatments for triple-negative breast cancer (TNBC) continue to improve, there is growing focus on issues that affect patients’ quality of life, including fertility preservation and treatment-related side effects. Dr. Nerea Lopetegui-Lia, a breast medical oncologist at The Ohio State University Comprehensive Cancer Center, recently discussed these concerns in an interview with OncLive®. She also highlighted the future of treatment options for TNBC, especially around recurrence and resistance.
Fertility Preservation for Younger Patients
TNBC primarily affects younger women, making fertility preservation a key consideration. Dr. Lopetegui-Lia emphasized the importance of addressing fertility before beginning cancer treatment, as chemotherapy, radiation, and surgery can lead to infertility or premature menopause. Early action is critical.
For male patients, sperm cryopreservation is the most effective method, although there are concerns about genetic damage if sperm is collected after treatment begins. In cases where semen samples cannot be provided, testicular sperm extraction is an option. Pre-pubertal males may consider experimental methods like testicular tissue cryopreservation, which is limited to clinical trials.
In females, the most common fertility preservation techniques are oocyte or embryo cryopreservation, which involve controlled ovarian stimulation and egg retrieval. For pre-pubertal girls, ovarian tissue cryopreservation is currently the only established option. Other experimental methods, like ovarian transposition or in vitro maturation, are emerging. Dr. Lopetegui-Lia advised that patients be referred to reproductive specialists for these procedures.
While gonadotropin-releasing hormone (GnRH) agonists are not a replacement for fertility preservation methods, they can be used as an adjunct during cancer treatment. GnRH agonists help reduce ovarian insufficiency and may modestly improve pregnancy rates.
Treatment-Related Toxicities
Managing the toxicities of TNBC treatments, including immune-related adverse events (irAEs), is a critical part of patient care. Immune checkpoint inhibitors (ICIs), such as pembrolizumab, can lead to severe irAEs that may be permanent or even fatal. While there is no reliable biomarker to predict these reactions, careful monitoring is essential.
In the phase 3 KEYNOTE-522 trial, irAEs were more common in patients receiving pembrolizumab, with 35% of patients reporting adverse effects compared to 13% in the placebo group. The most severe irAEs in the pembrolizumab group included skin reactions, hypophysitis, adrenal insufficiency, pneumonitis, and thyroiditis. Treatment for these effects often involves high-dose corticosteroids, which are tapered based on patient recovery. In cases of grade 4 toxicities, ICIs are discontinued, except in cases involving endocrinopathy, where hormone replacement is used.
Dr. Lopetegui-Lia also discussed newer treatments, such as antibody-drug conjugates (ADCs). For example, sacituzumab govitecan (Trodelvy) is associated with neutropenia and diarrhea, but prophylactic use of granulocyte colony-stimulating factor and loperamide can reduce these side effects. Fam-trastuzumab deruxtecan (Enhertu) is another ADC used in TNBC, but it requires regular monitoring for interstitial lung disease and left ventricular dysfunction.
The Future of TNBC Treatment
Despite promising initial responses, many patients with TNBC experience disease recurrence and metastasis, which underscores the need for new treatment strategies. Dr. Lopetegui-Lia pointed out the potential of combination therapies and biomarker-guided treatments to address these challenges. Overcoming treatment resistance is also a key area of research.
As new ADCs like datopotamab deruxtecan (Datroway) approach approval, attention is turning to whether these therapies can be used in sequence. Ongoing studies, such as the phase 2 TRADE DXd trial, are investigating the benefits of sequential ADC treatments with different targets, offering hope for more effective strategies in the future.
In conclusion, as TNBC treatments evolve, fertility preservation and managing treatment-related toxicities will remain critical to improving patients’ overall quality of life. The continued development of novel therapies and their sequencing will play a key role in addressing the challenges of recurrence and resistance in TNBC.
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