Endometrial Cancer Genetics

What Is Endometrial Cancer?

Endometrial cancer initiates with abnormal cell growth within the uterus, the pear-shaped organ in the pelvis where fetal development occurs. The cancerous growth begins in the lining of the uterus, known as the endometrium. Hence, it is also referred to as uterine cancer; although other forms, such as uterine sarcoma, exist, they are considerably less common. Endometrial cancer frequently manifests symptoms early on, typically presenting as irregular vaginal bleeding. Early detection often leads to successful treatment through surgical removal of the uterus, offering a cure in many cases.

Is Endometrial Cancer Genetic?

While endometrial (uterine) cancer is not directly inherited from mother to daughter, certain families carry a heightened susceptibility to this malignancy, particularly those with a history of Lynch syndrome.

Lynch syndrome typically stems from gene mutations like MLH1, MLH2, MLH5, MSH6, PMS1, PMS2, and TGBR2. These mutations hinder the body's ability to regulate cell growth and repair DNA damage, elevating the risk of endometrial cancer. Women with Lynch syndrome face a 40 to 60 percent likelihood of developing this cancer during their lifetime.

What Are the Types of Endometrial Cancer?

Endometrial cancer types are identified by examining cancer cells under a microscope:

• Type I: The most common type is endometrioid adenocarcinoma. These cells are linked to estrogen exposure, are less aggressive, and have a favorable prognosis.

• Type II: This category includes rarer subtypes like serous, clear cell, carcinosarcoma, and undifferentiated/dedifferentiated. They grow rapidly and are more likely to spread beyond the uterus.

Doctors may also classify endometrial cancer based on molecular subtypes, which offer insights into treatment outcomes:

• Copy number: High or low

• p53 mutation

• Mismatch repair (MMR) protein or microsatellite instability (MSI)

• DNA polymerase epsilon (POLE) mutation

• Human epidermal growth factor receptor 2 (HER2) amplification

Detailed information about the cancer cells helps doctors tailor the most effective treatment plan.

What Are the Other Risk Factors for Endometrial Cancer?

In addition to the genetic predispositions mentioned earlier, various factors can heighten a woman's likelihood of developing endometrial cancer, particularly those influencing hormone levels. For instance, increased risk is associated with:

• Hormonal Imbalances: Alterations in estrogen and progesterone levels influence changes in the endometrium, potentially heightening the risk of cancer. Conditions such as obesity, diabetes, and irregular ovulation patterns (common in polycystic ovary syndrome) can disrupt this hormonal balance. Moreover, postmenopausal hormone therapy containing estrogen and progestin may elevate the risk.

• Ovarian Tumors: Certain rare types of ovarian tumors that produce estrogen can also contribute to an increased risk of endometrial cancer.

• Prolonged Menstruation: Initiating menstruation before age 12 or experiencing menopause later in life raises the likelihood of endometrial cancer. The cumulative exposure of the endometrium to estrogen over the years of menstruation heightens the risk.

• Nulliparity: Women who have never been pregnant face a higher risk compared to those who have had at least one pregnancy.

• Advancing Age: Endometrial cancer predominantly occurs post menopause, with risk escalating as individuals age.

• Obesity: Excess body fat can disrupt hormone balance, increasing the risk of endometrial cancer.

• Hormone Therapy for Breast Cancer: Tamoxifen, a hormone therapy medication used for breast cancer treatment, can raise the risk of developing endometrial cancer. However, for most individuals, the benefits of tamoxifen outweigh the minimal risk of endometrial cancer.

How to Diagnose Endometrial Cancer?

Endometrial cancer often presents symptoms, aiding in its earlier detection and thereby improving prognosis. Unfortunately, there are no current preventive or early detection screenings for this cancer type. If one experiences symptoms, a gynecologist may conduct several tests to confirm the diagnosis:

• Pelvic exams involve examining the vagina, cervix, uterus, and ovaries for any abnormalities, including size and shape irregularities.

• Transvaginal ultrasound utilizes sound waves to create detailed images of the uterus and ovaries. This helps assess the thickness of the uterine lining and identify any tumors or masses.

• Endometrial sampling, or biopsy, entails removing a small tissue sample from the uterine lining during a pelvic exam. This sample is then analyzed by a pathologist to check for cancer cells.

While not a direct screening method for endometrial cancer, a Pap smear can sometimes indicate abnormalities in the endometrium. Pap smears involve collecting cells from the cervix to detect cervical cancer.

What Is the Treatment for Endometrial Cancer?

Treatment for endometrial cancer typically involves surgery, with additional therapies tailored based on the cancer type and the patient's health:

• Chemotherapy: Powerful drugs are used to kill cancer cells.

• Radiation therapy: Targeted radiation beams destroy cancer cells.

• Hormone therapy: Hormones are administered or blocked to treat cancer.

• Immunotherapy: Boosts the immune system to fight cancer.

• Targeted therapy: Medications target specific cancer cells to inhibit their growth.

Ongoing research aims to discover more effective treatment approaches for endometrial cancer.

Is Surgery Required for Endometrial Cancer?

Surgery serves as the primary treatment for endometrial cancer, typically involving a hysterectomy, which entails removing the uterus and cervix. There are four main types of hysterectomy procedures:

• Total Abdominal Hysterectomy: The surgeon accesses and removes the uterus through an incision in the abdomen.

• Vaginal Hysterectomy: The uterus is removed through the vagina.

• Radical Hysterectomy: If cancer has spread to the cervix, this procedure involves removing the uterus, adjacent tissues, and the upper part of the vagina.

• Minimally Invasive Hysterectomy: Multiple small incisions are made to remove the uterus, either laparoscopically or robotically.

During a hysterectomy, surgeons often perform additional procedures:

• Bilateral Salpingo-Oophorectomy (BSO): Removal of ovaries and fallopian tubes to ensure thorough cancer removal.

• Lymph Node Dissection (lymphadenectomy): Removal of lymph nodes to assess cancer spread.

Conclusion

In conclusion, endometrial cancer, originating from abnormal cell growth in the uterus, presents early symptoms such as irregular vaginal bleeding, facilitating timely detection. While not directly inherited, genetic predispositions, including Lynch syndrome, can heighten susceptibility. Understanding the cancer types, risk factors, and diagnostic procedures, such as pelvic exams and biopsies, is crucial for effective management. Surgery remains the primary treatment, often involving hysterectomy, supported by additional therapies tailored to individual cases. Ongoing research aims to enhance treatment efficacy and outcomes in combating this malignancy.