Two retrospective studies led by researchers in the United States and Italy report that women with HER2-positive breast cancers 1 cm or less in diameter that have not spread to the lymph nodes (“node-negative” tumours) have a risk of recurrence that is two to five times greater than that of women with HER2-negative breast cancers. The U.S. study also identified an increased risk of metastasis among women with small HER2-positive tumours, compared to those with HER2-negative tumours.

HER2-positive disease (in which tumours over-express the HER2 protein) is relatively uncommon in women with small, early-stage breast cancers, accounting for approximately 7 to 10 percent of the cases in these two studies. Women with small HER2-positive tumours are currently treated with lumpectomy followed by radiation. Some 25 percent of all breast cancers over-express the HER2 protein, which is known to be associated with a higher risk of recurrence and worse overall survival. In the U.S., trastuzumab is FDA-approved for the treatment of HER2-positive, node-positive disease and for women with node-negative disease with hormone (estrogen or progesterone) receptor-positive tumours who have another high-risk feature. Consensus guidelines, such as those from the National Comprehensive Cancer Network, currently do not recommend trastuzumab therapy for tumours less than 1 cm, due to a lack of prior supporting evidence.

Given these findings, the authors of both new JCO studies recommended that adjuvant anti-HER2 therapy with trastuzumab (Herceptin) be considered for patients with small, HER2-positive tumours. In an accompanying editorial, Harold J. Burstein, MD, PhD, and Eric P. Winer, MD, of Dana-Farber Cancer Institute and Brigham & Women’s Hospital, explained, “For the 15 to 20 percent of patients with HER2 over-expressing tumours, the success of trastuzumab has fast-forwarded our efforts and has led to a dramatic improvement in clinical outcomes.” Drs. Winer and Burstein added that while they agree that trastuzumab should be considered in this setting, additional therapy should generally be limited to patients with tumours 0.5 cm or larger and that abbreviated courses of adjuvant treatment be considered to minimize the risk of side effects.

Source: ASCO / JCO

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