Uterine Cancer: Let’s Broaden Our Knowledge

Uterine Cancer: Let’s Broaden Our Knowledge

This month, the Young Advisory Board (YAB) members will be addressing uterine Cancer. This cancer is sometime referred to as Endometrial cancer, which mainly affects postmenopausal women.  While uterine cancer is uncommon in women under the age of 45; YAB has found it important to write and share some general information with our readers. In 2015, the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program reported an estimated 54,870 women across the country were diagnosed with uterine cancer.  They also noted that this incidence is rising among all racial and ethnic groups. According to the CDC, uterine cancer is slightly more common in white women; however, black women are more likely to die from it. The story of the venerated journalist and anchor Gwen Ifill, who died at the age of 61 after being diagnosed a year earlier with a very aggressive type of Endometrial cancer, reminds us that learning about the symptoms and risk factors can help us identify the signs in someone close to us such as family members or friends.

 Source: CTCA

Some Facts about Uterine Cancer

  • It is the second most common gynecologic malignancy in developing countries and the seventh cause of cancer death among U.S. women. It is one of the five main types of gynecologic cancer among which cervical, ovarian vaginal and vulvar.

  • The most common type of uterine cancer is also called endometrial cancer because it forms in the lining of the uterus, called the endometrium.

  • All women are at risk for uterine cancer, but the risk increases with age. As we mentioned in our previous paragraph, most uterine cancers are found in women who are going through or who have gone through menopause. According to the American Cancer Society, the average age of women diagnosed with uterine cancer is 60.

  • The American Cancer Society estimates approximately 61,880 new uterine cancer diagnosis in the US for 2019 — about 12,160 women will die from it.

In terms of incidence and race, a recent CDC report found that black women were approximately twice as likely to die from uterine cancer as were women in other racial/ethnic groups [1]. African Americans experience higher rates of aggressive sub-types of uterine cancer (such as serous and clear, cell adenocarcinomas, and sarcomas) when compared to Caucasians, which might in part account for the higher death rate among black women. There is no conclusive explanation for this disparity. In an article from Gynecology Oncology, a group of researchers remarked that socioeconomic differences, equitable access to healthcare among minority patients can be attributed to such disparity [2].

Symptoms

Uterine cancer most often affects postmenopausal women, and the main symptom is spotting or bleeding. For premenopausal women, abnormal bleeding is usually the cardinal symptom, which is why irregular periods, heavy bleeding or constant spotting should never be ignored. Other symptoms may include pelvic pain, pain during intercourse, and unintended weight loss.

Risk factors

Most uterine cancers occur due to a hormonal imbalance that results in an abnormal buildup in the cavity of the uterus. In a normal menstrual cycle, women produce estrogen, which thickens the uterine lining. Ovulation, or the monthly release of an egg, triggers the production of progesterone, which prevents the uterine lining from getting too thick. Once a woman is no longer ovulating, the lining of the uterus gets blasted with estrogen but without the progesterone to balance it out, the potential for cancerous changes increases. Another major risk factor is obesity, which may highly increase the chance to get uterine cancer. Several other risk factors also include:

  • Taking estrogen by itself (without progesterone) for hormone replacement during menopause.

  • Taking Tamoxifen, a drug used to treat certain types of breast cancer.

  • Having close family members who have had uterine, colon, or ovarian cancer.

The table below reviews common risk factors for uterine cancer and their associated relative risk.

Uterine Cancer article table.png

BMI: body mass index; NA: RR not available.

Data from:

  • Smith RA, von Eschenbach AC, Wender R, et al. American Cancer Society guidelines for the early detection of cancer: Update of early detection guidelines for prostate, colorectal, and endometrial cancers. CA Cancer J Clin 2001; 51:38.

  • Setiawan VW, Yang HP, Pike MC, et al. Type I and II endometrial cancers: have they different risk factors? J Clin Oncol 2013; 31:2607.

Uterine Cancer and Obesity

The CDC states that uterine cancer is on the rise in the US, and has become one of the few cancers with increasing incidence and mortality. This trend is explained in part by the increase in the prevalence of people being overweight or obese [3, 4]. There is an emerging body of literature showing that obesity with a Body Mass Index (BMI) greater than 30 is responsible for up to 81% of the uterine cancer diagnosis. A study by Arem et al found that patients with BMIs of 30–35 had a higher risk of death compared to patients with BMIs of 25–29 [5]. There are three main hypotheses that could explain how obesity might contribute to cancer development and growth [4]:

  1. Fat cells increase the body mechanism that lead to the conversion of androgens (steroid hormone estrogen precursor) to estrogens and promote endometrial proliferation.

  2. The chronic inflammation associated with fat cells leads to hyperinsulinemia, and hyperglycemia, which also fuel endometrial proliferation.

  3. Inflammation and an increase in estrogen metabolites contribute to DNA damage and genetic instability.

These mechanisms are well illustrated below by this figure from cancer research UK.

uterine article pic2.jpg

In other words, fat cells stimulate the overproduction of estrogen, which causes the endometrial lining to thicken and grow out of control. This is why it is important to understand that obesity contributes to the increased risk of uterine cancer.

Genetic Burden

A gene mutation or genetic disorder may also increase the risk of uterine cancer. In our first blog post, we talked about BRCA gene mutations, which are associated with breast and ovarian cancer. Another genetic disorder that contributes to a high risk of cancer is hereditary nonpolyposis colorectal cancer, also known as Lynch syndrome. This condition increases the risk of colon cancer, ovarian cancer and uterine cancer. A recent review by Hinchcliff et al shows that the likelihood of developing uterine cancer is 20 percent to 60 percent, depending on the gene, as opposed to approximately 5% in the general population [6]. An identification of an inherited predisposition to developing cancer can allow a woman and her health care provider to make better informed decisions regarding screening, preventative interventions, and counseling of at-risk relatives. 

Recommendations

There is no known way to prevent uterine cancer. But these recommendations may help to reduce a woman’s chance of being diagnosed with uterine cancer:

For more information, please visit: https://www.cdc.gov/cancer/uterine/pdf/uterine_facts.pdf

References

  1. CDC - Uterine Cancer Incidence and Mortality — United States, 1999–2016

Weekly / December 7, 2018 / 67(48); 1333–1338

https://www.cdc.gov/mmwr/volumes/67/wr/mm6748a1.htm?s_cid=mm6748a1_w

  1. Long B, Liu FW, Bristow RE. Disparities in uterine cancer epidemiology, treatment, and survival among African Americans in the United States. Gynecol Oncol. 2013 Sep; 130(3): 652-9.

  2. Michaela A. Onstad, Rosemarie E. Schmandt, and Karen H. Lu, Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment. J Clin Oncol. 2016 Dec 10; 34(35):  4225–4230.

  3. Vicennati V, Garelli S, Rinaldi E, Rosetti S, Zavatta G, Pagotto U, Pasquali R. Obesity-related proliferative diseases: the interaction between adipose tissue and estrogens in post-menopausal women. Horm Mol Biol Clin Investig. 2015 Jan; 21(1): 75-87.

  4. Arem H, Park Y, Pelser C, et al. Prediagnosis body mass index, physical activity, and mortality in endometrial cancer patients. J Natl Cancer Inst. 2013; 105: 342-349. 

Hinchcliff EM, Bednar EM, Lu KH, Rauh-Hain JA. Disparities in gynecologic cancer genetics evaluation. Gynecol Oncol. 2019 Jan 30. pii: S0090-8258(19)30066-6.

Written by: RSP Young Advisory Board Members

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