Many newer agents in combination are being studied in the front-line treatment of women with HER2-positive metastatic breast cancer (MBC), but the story in the endocrine arena is more about the wise use of new strategies to overcome endocrine resistance, because no new antihormonal agents have been approved in the past decade. During his presentation at the NCCN 19th Annual Conference, Dr. William Gradishar explored what’s new in the treatment of MBC, focusing primarily on enhancing the effect of endocrine therapy to overcome resistance with newer targeted agents such as everolimus, reevaluating the role of rebiopsy on disease progression and measuring circulating tumor cells as a surrogate of response to treatment, and reviewing the effective treatment regimens for HER2-positive disease.
William J. Gradishar
William J. Gradishar
The management of advanced hormone receptor–positive disease has evolved with the emergence of CDK4/6 inhibitors. Improvements in progression-free survival of approximately 10 months were noted in pivotal trials of palbociclib. Strong efficacy was also seen with ribociclib, which was recently approved by the FDA. In the adjuvant treatment setting of hormone receptor–positive disease, an important issue for consideration is the duration of endocrine therapy.
William J. Gradishar
The treatment of HER2-positive breast cancer has benefited from a number of targeted agents. Although adjuvant trastuzumab has dramatically reduced progression—making metastatic disease far less common today—newer treatment advances are also impacting this disease. Dual targeting with pertuzumab and trastuzumab can extend the survival of metastatic disease by more 16 months, but despite such success, resistance to HER2 targeting remains a challenge. Drugs in the pipeline, such as neratinib, may help meet this therapeutic demand. In addition to anti-HER2 agents, chemotherapy is beneficial to patients with tumors 1 cm or larger, but the optimal treatment of smaller tumors is still a work in progress.
Presenter: William J. Gradishar
Systemic treatment for metastatic breast cancer now incorporates many targeted agents and a plethora of combinations specific to the breast cancer subtype. New to the treatment paradigm are fam-trastuzumab deruxtecan-nxki, and tucatinib for HER2-positive disease; the PI3K inhibitor alpelisib in combination with fulvestrant for estrogen receptor–positive and PIK3CA-mutated tumors; PARP inhibitors for patients with germline BRCA1/2 mutations; and the anti–PD-L1 agent atezolizumab in combination with albumin-bound paclitaxel for triple-negative disease with PD-L1 mutations in tumors. In addition, for estrogen receptor–positive disease, the role of CDK4/6 inhibitors increased substantially during the past year, as overall survival results have emerged. These targeted agents are greatly improving patient outcomes, and thus have all been incorporated into the NCCN Guidelines for Breast Cancer.
Mary Cianfrocca and William J. Gradishar
The question of combination versus single-agent chemotherapy in the setting of metastatic breast cancer (MBC) is an often-debated issue. Many single agents have activity in this setting and the potential for significant synergism between chemotherapy agents has led to many combination chemotherapy trials. This article defends the position that combination chemotherapy is the optimal approach for patients with MBC.
Virginia G. Kaklamani and William J. Gradishar
Presenters: Melinda L. Telli and William J. Gradishar
The recent approval of 4 agents for the treatment of patients with metastatic HER2-positive breast cancer has led to expanded recommendations in the NCCN Guidelines for treatment of this disease. For triple-negative disease, immunotherapy continues to gain traction in this challenging subtype, both in the preoperative and metastatic settings, though not yet as adjuvant treatment. Sacituzumab govitecan is another new agent with strong utility in triple-negative disease, and PARP inhibitors are recommended options in BRCA-mutated disease.
Melinda L. Telli, William J. Gradishar, and John H. Ward
Advances in molecular testing have ushered in the new era of precision medicine. The 2018 publication of the TAILORx trial helped refine the use of genetic expression assays, specifically the 21-gene recurrence score, in assigning patients to endocrine therapy alone or with chemotherapy. The NCCN Guidelines for Breast Cancer explore the clinical applications of this study. The algorithm for managing the axilla in early breast cancer has been further refined, based on the presence or absence of clinical evidence of lymph node involvement. Ovarian suppression has been validated as the optimal approach in higher risk premenopausal women, based on updated analysis of the SOFT and TEXT pivotal trials. In the metastatic setting, the NCCN Guidelines further reinforce the benefit of the CDK4/6 inhibitors, extending the “preferred” recommendation to all the available agents in metastatic disease. Options in triple-negative breast cancer now include, for the first time, an immunotherapeutic agent.
Sharon H. Giordano, Anthony D. Elias, and William J. Gradishar
The emergence of CDK4/6 inhibitors has changed the treatment algorithm for advanced/metastatic estrogen receptor–positive breast cancer. In pivotal trials of palbociclib, ribociclib, and abemaciclib, doubling in progression-free survival has been seen. All 3 agents in this class are now included in the NCCN Guidelines for Breast Cancer, and clinicians should be incorporating these agents into their treatment algorithms. The other important issue in this breast cancer setting is extended duration of endocrine therapy. Most of the benefit is modest and toxicity is an issue; therefore, extended-duration endocrine therapy should be highly individualized. For triple-negative disease, platinum agents and PARP inhibitors are helping some patients, but immunotherapies and other novel classes of drugs now in development hold the promise of even better outcomes. In HER2-positive early-stage disease, dual HER2 blockade is of modest benefit, and extended treatment with neratinib may be a good option for some high-risk patients.
Lauren Nye, Timothy K. Huyck, and William J. Gradishar
Breast cancer is the most common malignancy associated with pregnancy and is a rare but well-recognized complication. It is hypothesized that as more women continue to delay childbearing, the incidence of breast cancer in pregnancy will increase. Because of the lack of clinical experience with breast cancer in the setting of pregnancy, given its relative infrequency, many patients and physicians believe the diagnosis puts the life of the mother at odds with that of the fetus, but available data suggest that termination of the pregnancy does not improve the outcome for pregnant women with breast cancer. Often diagnosis is delayed because neither patient nor physician suspects malignancy. This report presents a recent case of a young primigravid woman with a newly appreciated breast mass seen at Northwestern University Feinberg School of Medicine as a means of discussing diagnostic considerations, therapeutic options, and supportive care available to the practitioner when managing a pregnant patient with breast cancer.