Lapatinib in the Treatment of Ductal Carcinoma in Situ of the Breast
Ductal carcinoma in situ (DCIS) of the breast is a pre-malignant lesion of the breast, which
is associated with a marked increase in the likelihood of developing invasive breast cancer.
Since DCIS tends to be associated with microcalcifications, it is detected with an increased
frequency in patients being screened with mammographic techniques. The treatment of DCIS is
based on a number of parameters; local treatment depends on the size of the lesion, grade
and margins. The only systemic treatment currently available is in the form of endocrine
therapy; it depends on the expression of estrogen receptor (ER). Randomized trials have
shown that the treatment of DCIS with breast conserving therapy and radiation is as
effective as simple mastectomy.
The efficacy of tamoxifen in reducing the incidence of further invasive or non-invasive
breast cancer has been established. In addition to surgery (with or without radiation),
patients with ER positive disease also receive anti-estrogen therapy. Current guidelines do
not recommend any additional therapy for ER-negative DCIS.
The rationale for the proposed study is based on the observations that HER2 is expressed at
high levels in higher grades of DCIS, which typically lack ER. In addition, an inverse
relationship between ER expression and the expression of EGFR has also been demonstrated.
Lapatinib is active against both these receptors and may have therapeutic action in ER
We propose to treat the patients with drug in the interval between biopsy diagnosis and
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
To identify gene signature that denotes effect of lapatinib therapy in breast cancer cell lines. To assess effect of lapatinib therapy in patients with ductal carinoma in situ of the breast using the gene signature developed as a surrogate marker.
Sunil Badve, MD
United States: Food and Drug Administration
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