What is the treatment for high-grade ductal carcinoma in situ (DCIS) that is GATA3 (GATA binding protein 3) and E-cadherin positive, with p63 (tumor protein p63) marking the myoepithelial cells?

From the Guidelines

The treatment for high-grade ductal carcinoma in situ (DCIS) that is GATA3 and E-cadherin positive with p63 marking the myoepithelial cells typically involves surgical excision as the primary approach, with breast-conserving surgery (lumpectomy) with clear margins often recommended, followed by whole breast radiation therapy to reduce the risk of local recurrence. For larger or multifocal DCIS, mastectomy may be necessary. After surgery, adjuvant endocrine therapy with tamoxifen (20 mg daily for 5 years) or an aromatase inhibitor like anastrozole (1 mg daily for 5 years) is often recommended for hormone receptor-positive DCIS to prevent recurrence, as shown in the NSABP B-24 trial 1. The positive GATA3 and E-cadherin markers indicate a luminal phenotype, suggesting hormone responsiveness, while the intact p63 staining of myoepithelial cells confirms the in situ nature of the disease without invasion. Some key points to consider in the treatment of DCIS include:

• The use of tamoxifen decreased all new breast events (HR, 0.71; 95% CI, 0.58–0.88; P=.002) in a phase III trial 1
• The IBIS-II trial demonstrated noninferiority of anastrozole to tamoxifen in women with ER-positive and/or progesterone receptor-positive DCIS treated by wide local excision with or without breast radiotherapy 1
• Treatment decisions should be individualized based on the extent of disease, patient age, comorbidities, and preferences, with the goal of preventing progression to invasive breast cancer while minimizing overtreatment. It is also important to note that follow-up of women with DCIS includes interval history and physical examination every 6 to 12 months for 5 years and then annually, and yearly diagnostic mammography, as recommended by the NCCN guidelines 1.

From the FDA Drug Label

Tamoxifen citrate tablets are indicated to reduce the risk of invasive breast cancer in women with DCIS, following breast surgery and radiation. The decision regarding therapy with tamoxifen for the reduction in breast cancer incidence should be based upon an individual assessment of the benefits and risks of tamoxifen therapy. Current data from clinical trials support 5 years of adjuvant tamoxifen therapy for patients with breast cancer In women with DCIS, following breast surgery and radiation, tamoxifen citrate tablets are indicated to reduce the risk of invasive breast cancer

The treatment for high-grade ductal carcinoma in situ (DCIS) that is GATA3 and E-cadherin positive, with p63 marking the myoepithelial cells, is tamoxifen citrate tablets for 5 years, following breast surgery and radiation, to reduce the risk of invasive breast cancer 2.

From the Research

Treatment for High-Grade DCIS

The treatment for high-grade ductal carcinoma in situ (DCIS) that is GATA3 and E-cadherin positive, with p63 marking the myoepithelial cells, typically involves surgical excision and may include radiotherapy and hormone therapy.

• Surgical treatment options include simple local excision to various forms of wider excision (segmental resection or quadrantectomy), or even mastectomy (either simple or skin-sparing) 3.
• Radiotherapy following breast-conserving surgery significantly reduces local recurrence rates 3, 4.
• The role of hormone therapy, such as tamoxifen or aromatase inhibitors, may be considered in the management of selected patients with DCIS, such as patients with hormone receptor positive DCIS 3, 5.

Factors Influencing Treatment

Several factors can influence the treatment of high-grade DCIS, including:

• The size and extent of the disease on mammography, with larger sizes increasing the risk of margin involvement and the need for further surgery 6.
• The presence of negative estrogen receptor status, which is associated with a higher risk of margin involvement 6.
• The grade of the disease, with high-grade disease being more likely to require mastectomy 6.

Additional Considerations

• Axillary lymph node dissection is not typically required for the management of DCIS, but sentinel lymph node biopsy may be considered in certain cases 3, 4.
• The use of minimally invasive methods, such as radiofrequency ablation, laser therapy, cryotherapy, and brachytherapy, is still being investigated and is not yet widely accepted as a standard treatment for DCIS 3.