Endometrial cancer is a cancer that starts in the lining of the uterus, called the endometrium. It is the most common cancer of the uterus, typically diagnosed in postmenopausal women at an average age of 60. Most cases are caught early because the disease produces a hard-to-ignore warning sign: abnormal vaginal bleeding. When found before it spreads, the five-year survival rate is nearly 95%.
How Endometrial Cancer Develops
The endometrium is a layer of tissue that thickens and sheds each month during menstruation. Endometrial cancer begins when cells in this lining start growing out of control. In most cases, the process is driven by prolonged exposure to estrogen without the balancing effect of progesterone. Estrogen stimulates endometrial cells to multiply. When that stimulation continues unchecked, the lining can progress from normal growth to overgrowth (called hyperplasia), then to precancerous changes, and eventually to cancer that invades deeper layers of the uterine wall.
Not all endometrial cancers follow this hormone-driven path. A smaller, more aggressive group arises from genetic mutations rather than estrogen exposure, developing in thin, inactive endometrial tissue. These cancers tend to behave differently and carry a worse prognosis.
Type I vs. Type II: Two Different Diseases
Doctors classify endometrial cancer into two broad categories that differ in almost every way: who gets them, how they grow, and how well they respond to treatment.
Type I (endometrioid carcinoma) accounts for the majority of cases. It is fueled by excess estrogen and tends to develop in women between 55 and 65 who have obesity, have never given birth, started their periods before age 12, or reached menopause later than average. Conditions like polycystic ovary syndrome and diabetes also increase risk. Under a microscope, these tumors still roughly resemble normal endometrial tissue. They are typically caught early and carry a generally good prognosis.
Type II (non-endometrioid carcinoma) is less common but more dangerous. It usually appears in older women, often between 65 and 75, and is not linked to high estrogen levels or obesity. These tumors look markedly abnormal under a microscope, with disorganized cells that may invade deeply through the uterine wall. Type II cancers are driven by different genetic mutations, particularly in the TP53 gene, and carry a generally poor prognosis. Black women are disproportionately affected by this type.
Risk Factors
The single thread connecting most endometrial cancer risk factors is estrogen. Anything that increases your lifetime estrogen exposure, or removes progesterone’s counterbalance, raises risk.
- Obesity: Fat tissue converts other hormones into estrogen. The higher your body mass index, the more estrogen your body produces. Obesity also lowers levels of a protein that binds estrogen and keeps it inactive.
- Hormone therapy without progesterone: Taking estrogen-only therapy for five or more years at least doubles the risk. Adding progesterone to the regimen eliminates this excess risk.
- Tamoxifen: This breast cancer medication acts like estrogen on the uterine lining. Using it for more than two years raises endometrial cancer risk by roughly 2 to 7.5 times, including an increased risk of aggressive subtypes.
- Reproductive history: Starting periods early, reaching menopause late, or never having children all extend the years your endometrium is exposed to estrogen.
- Lynch syndrome: This inherited genetic condition significantly raises the risk of several cancers, including endometrial cancer. Women with a first-degree relative who had endometrial cancer also face elevated risk.
Symptoms to Recognize
The hallmark symptom is abnormal vaginal bleeding, and it appears in the vast majority of cases. In the largest analysis of its kind, 90% of women diagnosed with endometrial cancer had reported bleeding before their diagnosis. For postmenopausal women, any vaginal bleeding is considered abnormal and worth investigating. For premenopausal women, unusually heavy periods or bleeding between periods can be a signal.
That said, most postmenopausal bleeding is not cancer. Among postmenopausal women who see a doctor for bleeding, roughly 9% ultimately receive an endometrial cancer diagnosis. The rest have benign causes like thinning tissue or polyps. But because early detection makes such a dramatic difference in survival, any unexplained bleeding justifies evaluation.
How It Is Diagnosed
Evaluation typically starts with a transvaginal ultrasound, which measures the thickness of the endometrial lining. A lining of 4 millimeters or less in a postmenopausal woman is reassuring. At a cutoff of 4 mm, ultrasound catches about 95% of endometrial cancers.
If the lining measures above that threshold, the next step is usually an endometrial biopsy. This is an office procedure where a thin, flexible tube is inserted through the cervix to collect a small tissue sample. For endometrial cancer specifically, this biopsy method has a sensitivity of about 75% and near-perfect specificity, meaning a positive result is highly reliable. If a biopsy cannot be performed or returns inconclusive results, a hysteroscopy (where a small camera is guided into the uterus to visualize the lining directly and take targeted samples) may be used instead. Hysteroscopy with tissue sampling detects endometrial cancer with about 86% sensitivity and over 99% specificity.
Staging and Survival
Once endometrial cancer is confirmed, staging determines how far it has spread. The system used is the FIGO staging framework, updated in 2023. In broad terms:
- Stage I: Cancer is confined to the body of the uterus.
- Stage II: Cancer has spread into the connective tissue of the cervix.
- Stage III: Cancer has spread beyond the uterus to nearby structures, such as the ovaries, fallopian tubes, vagina, or pelvic lining, or to regional lymph nodes.
- Stage IV: Cancer has spread to the bladder, bowel, or distant organs.
Survival rates reflect how critical early detection is. Data from the National Cancer Institute’s SEER program shows a five-year relative survival of 94.9% when the cancer is still localized to the uterus. That drops to 70.1% once it has reached regional lymph nodes, and to 19.9% when it has metastasized to distant sites. Because most women experience bleeding early, the majority of cases are diagnosed at the localized stage.
Treatment Options
Surgery is the cornerstone of treatment for most endometrial cancer. The standard operation removes the uterus, cervix, and usually both ovaries and fallopian tubes. For early-stage, low-grade cancers, surgery alone may be curative. Depending on the stage and tumor characteristics, radiation therapy may follow surgery to reduce the chance of recurrence in the pelvis.
For cancers that have spread beyond the uterus, chemotherapy becomes part of the treatment plan, typically using platinum-based drug combinations. Hormone therapy with progesterone-based medications can be effective for certain low-grade, hormone-sensitive tumors, and is sometimes used for younger patients who wish to preserve fertility before ultimately proceeding to surgery.
Immunotherapy has become an important option for advanced or recurrent disease. In 2021, the FDA approved a combination of an immune checkpoint inhibitor and a targeted therapy drug for patients with advanced endometrial cancer that has progressed after prior chemotherapy. In the clinical trial leading to that approval, 827 patients were enrolled who had already been treated with at least one platinum-based regimen. This combination is specifically used for tumors that lack certain DNA repair deficiencies. For tumors that do have those deficiencies (called mismatch repair deficient), immunotherapy alone has shown strong activity.
Protective Factors
Just as excess estrogen drives risk up, factors that reduce estrogen exposure or counterbalance it tend to be protective. Pregnancy and breastfeeding suppress ovulation and lower cumulative estrogen exposure. Combined oral contraceptives, which contain both estrogen and progesterone, reduce endometrial cancer risk, with the protective effect persisting for years after stopping. Maintaining a healthy weight is one of the most modifiable protective factors, since it directly reduces the body’s estrogen production. Physical activity independently lowers risk as well, in part by reducing obesity-related hormonal changes.