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HER2+ EBC: Evolution

CE / CME

The Evolving Therapeutic Landscape for HER2-Positive Early-Stage Breast Cancer

Pharmacists: 1.00 contact hour (0.1 CEUs)

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

Nurses: 1.00 Nursing contact hour

Released: August 10, 2020

Expiration: August 09, 2021

Lee Schwartzberg
Lee Schwartzberg, MD
CME/CE Information

Activity

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Course Completed

The Prognosis of HER2-Positive Disease Is Poor Without HER2-Targeted Agents

HER2-positive breast cancer is a specific subset of breast cancer that was identified several decades ago. HER2 is an oncogene that is a driver alteration: when overexpressed (which occurs in approximately 15% to 20% of newly diagnosed breast cancers), it drives those tumors to be more aggressive and to relapse more quickly. For patients who had HER2-positive disease before the availability of HER2-targeted agents, outcomes  were generally very poor, with most patients relapsing early.1 Clearly, in the absence of effective therapy, this is a very difficult and virulent type of breast cancer.

Thankfully, treatment regimens developed over the past 2 decades have markedly and rapidly changed outcomes for patients with HER2-positive breast cancer, both early-stage disease and after metastatic disease is detected. This is a testament to the fact that once the biology of a particular subgroup of cancer patients is elucidated, effective targeted therapy and treatment strategies can be developed to improve patient outcomes.

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Adjuvant Trastuzumab Improves DFS and OS for Patients With HER2-Positive EBC

The first major advance in the treatment of HER2-positive EBC was the use of the HER2 antibody trastuzumab. Large-scale adjuvant clinical trials in the early 2000s resulted in the establishment of HER2-targeted therapy as a standard of care in this setting. These trials, including HERA2-6; NCCTG N9831 and NSABP B31, which were analyzed together7-9; and BCIRG 006,10,11 all showed that adding 1 year of trastuzumab therapy to standard adjuvant chemotherapy regimens improves disease-free survival (DFS) and, ultimately, OS for patients with HER2-positive EBC.

These studies showed a dramatic improvement in survival with adjuvant trastuzumab that was consistent across the different patient populations enrolled in each study as well as with using different chemotherapy backbones and different treatment strategies. Across studies, there was an approximate improvement of 25% to 40% in both DFS and OS with the addition of trastuzumab to the standard chemotherapy regimens used in each trial. Based on these and other studies in the metastatic setting, 1 full year of trastuzumab has become a standard of care for HER2-positive EBC.

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Risk Factors for Recurrence of HER2+ EBC Treated With Trastuzumab-Based Therapy

We now understand more about the risk factors for recurrence of HER2-positive EBC in patients who are treated with standard chemotherapy and trastuzumab. Dall and colleagues12 conducted a prospective study on routine trastuzumab use for 6 years in Germany and, as expected, patients with larger primary tumors had a worse outcome. This analysis showed that, as in all other subgroups of breast cancer, patients with more advanced anatomical disease (ie, node positive disease) have a significantly higher risk of recurrence. Of interest, patients who had hormone receptor–negative EBC had a lower risk of recurrence than hormone receptor–positive patients. This has been seen in other datasets as well.

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