Up to 25 percent of breast cancers overexpress the HER2/neu gene. The majority of HER2+ tumors are estrogen receptor negative (ER-) and progesterone receptor negative (PR-). HER2+ disease is associated with a significantly higher rate of local breast cancer recurrence (i.e., in the same breast as the original tumor) as HER2- disease. Therefore, breast cancer patients with HER2+ multifocal disease may not be good candidates for lumpectomy or other breast conserving surgery. Obesity appears to predict worse outcomes in HER2 positive (HER2+) patients.
The development of Herceptin, which is used to treat HER2+ breast cancer, has markedly improved the prognosis of this type of breast cancer. HER2+ tumors have a greater tendency to metastasize first to the liver and lungs than other breast cancer subtypes.
Herceptin (trastuzumab) is a monoclonal antibody used to treat HER2/neu overexpressing breast cancer. Herceptin binds selectively to the HER2 protein, thereby reducing cancer cell growth and proliferation. Herceptin has been shown to be effective in reducing breast cancer recurrence even among women with lower risk breast cancer (small, early stage, lymph node-negative disease). Herceptin normally is administered intravenously alone or in combination with chemotherapy. Use of Herceptin can lead to heart damage, especially when used in conjunction with an anthracycline chemotherapy regimen. Herceptin used in conjunction with nonanthracycline chemotherapy regimens has had some success to treat HER2+ breast cancer with fewer acute toxic effects and lower risk of cardiotoxicity. However, this combination has not been shown convincingly to be as effective as anthracycline-based regimens.
There are a few foods and spices that have been shown to amplify the effects of Herceptin, thereby increasing its effectiveness. Please see our article on Herceptin.
Inflammation and HER2+ prognosis
Systemic inflammation promotes breast cancer growth, invasion and metastasis. Inflammation, as measured by circulating C-reactive protein (CRP), has been found to reduce survival among breast cancer patients in general and HER2+ patients in particular. Inflammation may also contribute to resistance to Herceptin.
High BMI and diabetes and HER2+ prognosis
Obesity is linked to worse outcomes in HER2+ patients. Chronic exposure to leptin, a hormone correlated with excess fat, increases HER2 stability. Leptin can impair response to Herceptin in breast cancer cells. However, recent evidence suggests that treating with Herceptin concurrently with chemotherapy may potentially equalize disease free survival rates between obese and normal weight women with HER2+ breast cancer.
Type 2 diabetes is a significant risk factor for developing breast cancer and breast cancer progresion. There is some evidence that the risk of HER2+ breast cancer is heightened by diabetes even in the absence of obesity. High circulating insulin levels increased both the tumor size and number of lung metastases in a mouse model of HER2+ breast cancer in one study. Use of metformin is associated with better prognosis among women with HER2+ breast cancer.
HER2 status changes
Several studies have reported that HER2 status can differ between a primary tumor and its lymph node metastases (known as discordance) and that the status can continue to change during disease progression. In other words, a woman with an HER2+ breast tumor can have HER2- lymph node metastases and vice versa. This happens in approximately 15% of cases. The possibility of discordance indicates a need to take biopsies and assess HER2 and hormone receptor status during disease progression in order to optimize treatment decisions.
One study found that HER2 expression can vary within an initial primary tumor and that this predicts shorter disease-free survival than consistent HER2 gene amplification. This appears to be more common when the biopsy results indicate low-grade HER2 amplification or questionable HER2 expression. Such findings indicate a need for HER2 testing on larger tumor samples for accurate assessment of HER2 status, according to the authors.
We have elected not to try to summarize the statistics concerning risk of recurrence for HER2+ disease here because it varies greatly depending on numerous factors. Specific data concerning relapse and survival can be found in the studies below.
Below are links to recent studies on this topic. For a more complete list of studies, please click on HER2+. Please also see our articles on HER2/neu overexpressing disease (which describes this type of breast cancer) and breast cancer diet for HER2+ patients and survivors.