Breast Cancer And Uterine Cancer Connection

Frequencies Of Invasive Endometrial Procedures In Breast Cancer Survivors

The frequencies of invasive endometrial procedures were higher in the TAM groups than those in the non-TAM subgroups . Among the TAM group aged 60 years or more, invasive endometrial evaluations and D& C were performed about 18 and 23 times to detect one endometrial cancer, respectively. However, in the TAM group aged below 40 years, invasive endometrial evaluations and D& C were conducted more than 46 and 54 times to find one endometrial cancer, respectively.

Table 4 Frequencies of endometrial procedures in breast cancer survivors 1 year after initiation of treatment.

Figure 2 Procedure-free probability in breast cancer survivors by tamoxifen and age at diagnosis. Endometrial evaluation, Dilatation and Curettage.

Among breast cancer survivors treated with TAM, the rates of invasive endometrial procedures were higher in subjects with benign endometrial conditions . Among the TAM-treated subjects with benign endometrial conditions, the ratios of the frequency of invasive diagnostic procedures to the incidence of endometrial cancer were 49.0 and 59.5 in subjects under 40 years. However, in subjects aged 60 or more, the ratios were 14.6 and 21.2 , respectively.

D Effect Of Pregnancy On Leiomyoma

The effect of pregnancy on fibroids has been controversial. Despite the dramatic elevation in the circulating ovarian steroid levels, there is no conclusive evidence to explain the change in size of fibroids during pregnancy . However, the majority of longitudinal studies were performed in patients who were found to have fibroids on their obstetrical ultrasounds at the 16th to 18th weeks , whereas the greatest increase in the volume of uterine leiomyoma occurred before 10 wk gestation . Considering that cellular hypertrophy significantly contributes to tumor growth, the longitudinal studies that were conducted in the second and/or third trimesters likely missed this window of tumor volume increase in response to elevated progesterone levels. Hence, the absence of detectable growth in fibroids during pregnancy does not necessarily contradict the model of progesterone-dependent fibroid growth.

What Is Endometrial Cancer

The lining of the uterus is called the endometrium. Cancer of the endometrium is the most common cancer of the female reproductive organs.

Cancer of the endometrium is different from cancer of the connective tissue or muscle of the uterus, which is called uterine sarcoma. About 80 percent of all endometrial cancers are adenocarcinomas. This means the cancer occurs in the cells that develop the glands in the endometrium. Endometrial cancer is highly curable when found early.

Uterine carcinosarcoma is a very rare type of uterine cancer, with characteristics of both endometrial cancer and uterine sarcoma. It is also known as a malignant mixed mesodermal tumor.

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Does Estrogen Cause Cancer

Estrogen plays a role in causing certain cancers.

Cells in your body have hormone receptors. The hormone receptors are a type of protein. Estrogen in your bloodstream can attach to the receptors. This hormone-receptor process is part of typical body function. In healthy cells, estrogen aids normal cell function and growth.

Today, experts know that several different factors play a role in turning healthy cells cancerous. When these factors are present, estrogen can act as a spark. The hormone causes cancer cells to multiply and spread.

What Questions Should I Ask My Doctor

You may want to ask your healthcare provider:

• Is the cancer estrogen-dependent or hormone-receptor-positive?
• What is the best treatment for this type of cancer?
• What are the treatment risks and side effects?
• What changes can I make to protect my health?
• Should I use a different form of birth control?
• Can I use hormone therapy?

A note from Cleveland Clinic

Most of the time, estrogen plays a positive role in healthy body functions. Estrogen-dependent cancers are an exception. In these cancers, estrogen fuels cancer growth. If you develop a cancer that could be hormone-sensitive, your healthcare provider will do tests to find out if its related to estrogen. This information helps your healthcare provider select the most effective treatment for you.

Last reviewed by a Cleveland Clinic medical professional on 09/10/2021.

References

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How Is Endometrial Cancer Detected

An endometrial biopsy is the most commonly used test for endometrial cancer and is very accurate in postmenopausal women. It can be done in the doctors office. A very thin, flexible tube is put into the uterus through the cervix. Then, using suction, a small amount of endometrium is removed through the tube.

C Permissive Role Of Estrogen To Enhance Progesterone Action

In vivo, human fibroid cells are embedded in thick layers of extracellular matrix , which has been shown to influence critical cellular functions . The fibroids in animal models appear to lack the characteristic of ECM overproduction in human fibroids, suggesting a fundamental difference in their nature compared with the human tumor. The absence of the organotypic ECM may also underlie the dramatic changes in gene expression patterns in human fibroid cells grown on plastic dishes and for the discrepancy in progesterone actions in vivo and in vitro. An improved method that fills the gap between clinical and in vitro studies is the xenograft model, in which tissue fragments of human fibroids are placed under the subrenal capsule of immunodeficient mice . Surprisingly, the growth of fibroid xenografts depended on the combination of estradiol and progesterone, whereas estradiol or progesterone alone was unable to stimulate growth. Although estradiol is not a mitogen by itself, it is essential for the expression of PR, thereby supporting the progesterone action on fibroid cells .

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The Nci Bcddp Follow Up Study

The Breast Cancer Detection Demonstration Project , sponsored by the American Cancer Society and the National Cancer Institute , was a breast cancer screening programme conducted between 1973 and 1980. The BCDDP provided up to five annual breast examinations to 283 222 women at 29 screening centres in 27 cities throughout the United States. Over 99% of the participants were between the ages of 35 and 74 when they entered the screening programme, with a median age of 50 years. The NCI began a follow up study of a subset of the BCDDP participants in 1979, which included all women who were diagnosed with breast cancer during the BCDDP all women who had breast surgery performed during the screening programme with no evidence of malignant breast disease all women who had received a recommendation by the project for a surgical consultation, but who did not have either a biopsy or aspiration performed and a sample of women who were not recommended for surgical consultation and did not undergo a biopsy .

Estrogen Receptor Mutations Cause Estrogen

Mutations in the LBD of ER were initially reported over two decades ago in breast cancer cells and tumors . However, they remained a relatively underexplored phenomenon until recently. The advent of newer generation, deep sequencing technologies has led to the discovery of ER mutations in approximately 15% of metastatic ER-positive breast tumors . Although other ER mutations have been identified at lower frequencies, the most predominant LBD mutations occur within helix 12, mainly affecting three amino acids in that region: L536, Y537, and D538. Studies have shown a clear association between these heterozygous, activating mutations and acquired hormone therapy resistance . Interestingly, the mutations are observed in less than 1% of primary breast tumors and are not thought to drive breast tumor initiation . ER mutations are more prevalent in primary endometrial cancer, with 5.8% of tumors harboring an ER mutation , representing approximately 3500 new ER mutant endometrial cancer diagnoses in the USA each year.

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Managing Endometrial Cancer Risk

• having taken postmenopausal hormone replacement therapy
• never having had children
• early menstruation and/or late onset of menopause
• polycystic ovarian syndrome
• hereditary nonpolyposis colorectal cancer syndrome, or HNPCC

• lose weight as needed
• eat a healthy, low-fat diet
• exercise regularly
• if you have diabetes, keep it under control

What Is The Link Between Estrogen And Uterine Cancer

Uterine, or endometrial, cancer forms in the lining of your uterus. Women are more likely to develop this cancer after menopause.

Your estrogen-related risk may go up with:

• Estrogen replacement therapy: Estrogen eases menopausal symptoms like hot flashes, night sweats and vaginal dryness. But taking estrogen alone increases the risk of uterine cancer. Combination hormone therapy is less likely to cause uterine cancer. If youve had a hysterectomy, you dont have a uterus and cant get uterine cancer.
• Tamoxifen: Tamoxifen is a breast cancer drug that lowers the risk of breast cancer and breast cancer recurrence. Its a selective estrogen receptor modulator that blocks estrogens effects on breast tissue. But in menopausal women, tamoxifen acts like estrogen in your uterus. It stimulates the growth of your uterine lining, increasing endometrial cancer risk. Still, the chances of developing endometrial cancer from tamoxifen are less than 1% per year. Theres also a slightly higher risk of uterine sarcoma, a cancer that forms in uterine muscles or tissues.

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Breast Cancer And Uterine Fibroids

Although uterine fibroids and breast cancer may seem to be extremely different diseases, they have a few similar factors such as how they are influenced by hormone production. Studies have also shown that a womans risk of breast cancer is related to how much estrogen and progesterone her body is producing. Over time, being exposed to high levels of these hormones, especially estrogen, has been linked to an increased risk of estrogen-positive breast cancer, which is the most common. Just like uterine fibroids, estrogen-positive breast cancer can be caused by genetic and lifestyle factors such as:

• Excessive alcohol consumption, which increases folic acid levels.
• Increased body mass index or obesity after menopause.
• Family history.
• Lack of physical activity.

All of these factors increase your risk of estrogen-positive breast cancer as well as fibroids. This is because these lifestyle and genetic risks can influence the levels of estrogen your body produces. Consult your physician if you have questions about your individual fibroid or breast cancer risk. Your doctor can help you navigate with receiving a diagnosis and finding a treatment plan that works for you. Both uterine fibroids and breast cancer symptoms should never be ignored. Dont wait for changes to worsen, get ahead of them before they progress.

Endometrial Cancer Incidence In Breast Cancer Patients Correlating With Age And Duration Of Tamoxifen Use: A Population Based Study

Ju-Yin Chen1,2, Shou-Jen Kuo2, Yung-Po Liaw3, Itzhak Avital4, Alexander Stojadinovic4, Yan-gao Man4, Ciaran Mannion5, Jianlian Wang6, Ming-Chih Chou7,8, Horng-Der Tsai9, Shou-Tung Chen2 , Yi-Hsuan Hsiao7,9

1. Department of Epidemiology, School of Public Health, University of California Los Angeles, USA.2. Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan.3. Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan.4. Bon Secours Cancer Institute, Bon Secours Health System, Richmond, VA, USA.5. Department of Pathology, Hackensack University Medical Center, Hackensack, NJ, USA.6. Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.7. School of Medicine, Chung Shan Medical University, Taichung, Taiwan.8. Division of Thoracic Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.9. Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan.

Citation:J Cancer

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A Clinical Evidence For The Role Of Progesterone In The Breast

The human mammary gland consists of a series of branching ducts composed of luminal epithelial cells that line the central lumen and underlying myoepithelial cells that are adjacent to the basement membrane. Surrounding this epithelium is a collagenous stroma and adipose tissue. Estrogen and progesterone are essential for the development of the breast and actively promote cell proliferation during ductal development and pregnancy. As is the case for uterine fibroids, estrogen has been considered to be the primary mitogenic factor in the mammary gland. There is a wealth of evidence to support the critical role estrogen plays in the breast and its involvement in the pathogenesis of breast cancer . Comparatively, the role of progesterone in the human adult mammary gland and in cancer is less clear. However, preclinical and clinical evidence have demonstrated the pro-proliferative and antiproliferative roles of progesterone in the adult breast and breast cancer through autocrine and paracrine actions between PR-positive and PR-negative mammary cells. Recent studies have also demonstrated that progesterone expands a stem cell population that is sensitive to transformation .

Uterine Sarcoma Risk Factors

It is not yet known what causes most uterine sarcomas, but certain risk factors have been known to play a role. Risk factors for uterine sarcoma include:

Radiation therapy to the pelvic area: Such treatments, typically to target a different cancer type, increases a womans risk of uterine cancer later. Radiation damages even healthy cells, which may lead to cancer. Uterine sarcomas that develop because of radiation exposure typically occur five to 25 years after the treatment.

Race: Uterine sarcomas are about twice as common in African-American women as they are in white or Asian women.

History of retinoblastoma: This type of eye cancer is caused by an abnormal gene and is linked to a higher risk of uterine sarcoma.

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Is There A Relationship Between Pregnancy And Breast Cancer Risk

Studies have shown that a womans risk of developing breast cancer is related to her exposure to hormones that are produced by her ovaries . Reproductive factors that increase the duration and/or levels of exposure to ovarian hormones, which stimulate cell growth, have been associated with an increase in breast cancer risk. These factors include early onset of menstruation, late onset of menopause, and factors that may allow breasttissue to be exposed to high levels of hormones for longer periods of time, such as later age at first pregnancy and never having given birth.

Conversely, pregnancy and breastfeeding, which both reduce a womans lifetime number of menstrual cycles, and thus her cumulative exposure to endogenous hormones , are associated with a decrease in breast cancer risk. In addition, pregnancy and breastfeeding have direct effects on breast cells, causing them to differentiate, or mature, so they can produce milk. Some researchers hypothesize that these differentiated cells are more resistant to becoming transformed into cancer cells than cells that have not undergone differentiation .

C Progesterone Action In Breast Cancer Cells

Progesterone action in normal mammary epithelium is distinct from that in breast cancer. Microarray analyses have shown that different pathways are regulated by progesterone in normal breast cells vs. breast cancer cells, with little overlap . It is thought that progesterone/progestins are able to both inhibit and stimulate proliferation of breast cancer cells. Unlike the paracrine action of progesterone in normal breast epithelial cells, there is an increase in the number of proliferating cells that are ER/PR-positive in breast cancer cells . In addition, it has been observed in clinical samples that there is an increase in the percentage of proliferating ER/PR-positive cells in areas of normal tissue in breast cancer patients, in hyperplasias, and in ductal carcinoma in situ, which correlates with an increased risk of developing breast cancer . Thus, a switch from paracrine- to autocrine-regulated progesterone action occurs upon neoplastic transformation of cells, leading to breast cancer .

In advanced breast cancer, studies have suggested that progesterone may be inhibitory or suppressive in proliferation, invasion, metastasis, and inflammation processes . Furthermore, unliganded PR has been shown to suppress growth and inflammatory responses in breast cancer cells .

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What You Need To Know

• Endometrial cancer starts in the lining of the uterus the endometrium.
• Being overweight or obese greatly increases a womans chance of developing endometrial cancer. Other risk factors include age, family history, a diagnosis of polycystic ovary syndrome and prior use of the breast cancer treatment drug tamoxifen.
• Symptoms include abnormal vaginal bleeding, pain during intercourse, difficult or painful urination, and pain in the pelvic area.
• Endometrial cancer is highly treatable when found early.

Does Fertility Treatment Affect The Risk Of Breast Or Other Cancers

Women who have difficulty becoming pregnant or carrying a pregnancy to term may receive fertility treatment. Such treatment can include surgery medications to stimulate ovulation and assisted reproductive technology.Ovarian stimulation and some assisted reproductive technologies involve treatments that temporarily change the levels of estrogen and progesterone in a womans body. For example, women undergoing in vitro fertilization receive multiple rounds of hormone treatment to first suppress ovulation until the developing eggs are ready, then stimulate development of multiple eggs, and finally promote maturation of the eggs. The use of hormones in some fertility treatments has raised concerns about possible increased risks of cancer, particularly cancers that are linked to elevated levels of these hormones.Many studies have examined possible associations between use of fertility drugs or IVF and the risks of breast, ovarian, and endometrial cancers. The results of such studies can be hard to interpret because infertility itself is linked to increased risks of these cancers . Also, these cancers are relatively rare and tend to develop years after treatment for infertility, which can make it difficult to link their occurrence to past use of fertility drugs.

Selected References

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What Is The Link Between Estrogen And Breast Cancer

About 8 out of 10 breast cancers are hormone receptor-positive. These cancers need estrogen, progesterone or both hormones to grow. Excess exposure to estrogen raises cancer risk. Excess exposure can occur because of:

• Hormone replacement therapies for menopause.
• Naturally high estrogen levels.
• Klinefelter syndrome, a genetic condition affecting men.

In the past, some men took estrogen to treat prostate cancer. Healthcare providers rarely use this treatment now because it increases the risk of male breast cancer.