The Targeted Drug Trastuzumab for Serous Endometrial (Uterine) Cancer Treatment

Endometrial (uterine) cancer is the most common gynecological cancer in Türkiye and developed countries. Worldwide, per 100 thousand women, 8 are newly diagnosed annually; in our country, per 100 thousand women, 6 new endometrial cancer cases occur. In developed countries, annual incidence can reach, per 100 thousand, 25 new cases. Around 2000 women develop uterine cancer and around 500 die of it each year in our country. The risk of endometrial cancer by age 75 is estimated at % 1.7. Median age at occurrence is 60.

The endometrium is the uterus's innermost layer. Because most uterine cancers develop there, uterine cancer means endometrial cancer unless otherwise specified.

- Related topic: Uterine Cancer Stages and Treatment (in Detail)

Endometrial cancers are divided into two main groups: 

• % 80-90 are type 1 endometrial cancer
• Fewer than %20 are type 2 endometrial cancer: this rare type 2 has two subtypes, serous papillary carcinomas and clear cell carcinomasas the subtypes.

The rare serous papillary and clear cell endometrial cancers tend to occur in older patients but are more aggressive subtypes; more than %50 of endometrial cancer deaths are due to tumors of these 2 subtypes.

The common subtype, type 1 endometrial cancer, arises from prolonged estrogen exposure. It is generally detected earlier, has a better course and is associated with obesity.

- Related topic: How Does Obesity Increase Uterine Cancer Risk? (in Detail)

Serous papillary and clear cell endometrial cancers are thought to develop independently of estrogen, and these cancers' association with the p53 tumor suppressor gene and HER2 gene mutations is known.

Chemotherapy is currently standard treatment for serous endometrial cancer. However, in around %30 of serous endometrial cancers, involved in cell growth and proliferation, the HER2 receptoris known to be overexpressed on the cell surface. This led to drugs blocking this receptorbeing tested for serous endometrial cancer treatment. For this purpose, a phase-2 clinical trialenrolled stage 3, stage 4 or recurrent, HER2-positive patients, totaling 61 with serous endometrial cancer.

Patients were randomized into two arms, one receiving standard chemotherapy (carboplatin+paclitaxel), the other chemotherapy plus the anti-HER2 targeted drug trastuzumab. Trastuzumab (original brand name Herceptin) is a monoclonal antibody that binds HER2 and prevents the receptor from transmitting growth/proliferation signals into the cell.

At the study's end, it was found that;

• In the group with an anti-HER2 drug added, median progression-free survival (the time treatment keeps disease controlled) was significantly longer (12.6 months versus 8 months).
• The progression-free survival advantage was more pronounced among stage 3 and 4 patients receiving treatment for the first time: 17.9 versus 9.3 months.
• Adding trastuzumab to chemotherapy also did not increase adverse effects.

According to this clinical trial, assessing HER2 positivity in patients with serous endometrial cancer appears appropriate, just as we currently do in all breast cancer patients. This could provide a new treatment that improves outcomes in this aggressive and rare cancer type, for which treatment options are limited.