The history that is compatible with endometrial cancer is number one, postmenopausal bleeding. I think that is fairly obvious for most gynecologists who have a patient present in their office who say, I am bleeding. There are other causes for postmenopausal bleeding, but the first flag in your head should be, this may be coming from her uterus, therefore we should get an endometrial biopsy. Certainly, there are other sources of postmenopausal bleeding that can be coming from the bladder, the rectum, vagina, atrophy and those sources need to be worked up. Abnormal menses is a much more difficult diagnosis to make, and you have to be very astute to your patient’s menstrual history and really listen, my periods are increasing, they are coming twice a month, I’m spotting in between the month, this is a group of patient’s that you really have to be on the ball to pick up, because this is the group that gets missed, the 25% that are before menopausal or perimenopausal frequently get diagnosed in a later stage of disease, simply because they were told they are perimenopausal, they have been put on progesterone therapy, oral contraceptions and not undergone an endometrial sampling or even a pelvic ultrasound to diagnose whether there is a thickened endometrial stripe or even a suspicious stripe.
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Only 20% of patient’s who present with postmenopausal bleeding will ultimately have a malignancy, however, the older the patient that presents with postmenopausal bleeding, the more likely she is to have an endometrial cancer. The diagnosis of endometrial cancer is simple, we need to get a specimen of the endometrial cavity, the gold standard is a fractional D&C, most of the fractional D&Cs can be avoided by the office biopsy. I tend to use a Randall curette which is the exact same diameter as a Pipel, except it’s metal, so it doesn’t bend, so as far as the discomfort, because of the cervical dilatation, it’s exactly the same as the Pipel, but sometimes in the postmenopausal woman, it’s a little more difficult to get into the cervical os so I find that the Randall Pipel without the teeth works very well. In addition, if you use the Randall Pipel because it’s metal, you can actually sound the uterus and decide how large it is, you can actually feel where you are with your endometrial sample.

The last diagnosis of endometrial cancer is occasionally picked up on an asymptomatic woman which again is very rare to have a patient who has endometrial cancer who is asymptomatic, but it does occur, to pick it up on a Pap smear. If you have 100 patient’s that have endometrial cancer and you took Pap smears from those patient’s, only 20 would have an abnormal Pap smear. Of the 20 that have an abnormal Pap smear, about 80% would be AGUS, meaning atypical glandular cells of undetermined significance, not ASCUS, atypical squamous cells of undetermined significance, if you ever have a patient in your practice that has atypical glandular cells, those patient’s really need to be worked up thoroughly with an endocervical curettage plus an endometrial curettage, but the Pap smear is not designed to pick up endometrial cancer, it designed to pick up precancerous lesions and does a very poor job for screening for endometrial cancer. The office biopsy is 90% accurate, meaning if you can gain access to the endometrial cavity and you have a patient that has endometrial cancer, 90% of the time it will give you the answer that you have a cancer, 10% of the patient’s who truly do have a cancer that you have done the office Pipel or Randall curette, whatever your choice, 10% of those patient’s will be missed. So therefore, it is imperative that patient’s who have abnormal uterine bleeding that you strongly suspect need to be worked up to rule out an endometrial cancer in your office, biopsy comes back negative. For those small percentage of patient’s, the 10%, they really should undergo a formal procedure, a D&C if that’s medically possible. There are other ways of diagnosing endometrial cancer, one of the new advances has been hysteroscopy which is used on conjunction with D&C and I think this is a very nice technique, it can pick up polyps which you can miss on your D&C, you can also look at the endocervical canal, occasionally you can be working somebody up for an endometrial cancer and find out that indeed they had adenocarcinoma of the endocervix and it not from the endometrium, so I think that hysteroscopy does add t the D&C, it’s not absolutely necessary for complete workup of endometrial cancer, it’s just a diagnostic tool. Hysteroscopy is very infrequently used, it’s used in conjunction with ultrasound. It’s a technique where they look with the ultrasound machine at the uterine strip, and they place saline in to see if this is a cancer. If you’re going to go to that extreme, at some point you are still going to have to sample the patient with either an office biopsy or fractional D&C so I’m not sure that the added expense of this test is always indicated.

Everybody in this room is probably familiar with the risk factors of endometrial cancer, the number one risk factor would be obesity in the postmenopausal group, the reason for obesity being a risk factor is as androstene dione is peripherally converted to estrone in the adipose tissue, so the more adipose tissue you have, the potential for more estrone production you have, therefore more stimulation of your endometrial cavity. Nulliparity has always been a risk factor for endometrial cancer, it is unclear whether it’s because patient’s who do develop endometrial cancer may be anovulatory or they have no interruption of their hormonal stimulation of their endometrium. It has been shown that women who have been on oral contraceptives for at least 12 months at some point during their life, have a protective mechanism against endometrial cancer, so they feel that nulliparity is probably a lack of interruption of the constant estrogen stimulation of the endometrium.

If we look at late menopause again, this is a subjective symptom, sometimes you will have women who come in and say, well I have been bleeding and their 65 years old, well obviously they haven’t gotten with the program that they are having abnormal bleeding, they have gone through the change but they are having abnormal bleeding. Diabetes and hypertension is disease processes that are associated with the elderly and also associated with the obese. So it’s unclear whether diabetes and hypertension actually have a cause and effect relation with endometrial cancer, they tend to present with the patient package of an elderly patient who is overweight, who has adult onset diabetes and therefore has adult onset hypertension caused from her obesity. The number one risk factor for endometrial cancer is unopposed estrogen, and this is for the garden variety endometrial cancer, adenocarcinoma, it does not hold true for papillary or clear cell carcinomas, the run of the mill adenocarcinoma is associated with unopposed estrogen.
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In recent years, there has been a lot of use with tamoxifen therapy in breast cancer prevention and in patient’s who have breast cancer to prevent the other breast from receiving tamoxifen in order to be protective against receiving another breast cancer in the opposite breast. There has been a lot of controversy in the literature saying that if you are on tamoxifen, your risk of developing endometrial cancer is seven times that of normal, and indeed that is true. However, of all the patient’s if you take 1000 patient’s who are on tamoxifen therapy for breast cancer prevention, out of the thousand, only two will develop endometrial cancer, therefore, 998 patient’s who are on tamoxifen will not get endometrial cancer. The type of endometrial cancer that patient’s get while they are on tamoxifen is exactly identical to what they get if they are not on tamoxifen. The present with postmenopausal bleeding and therefore, have an early warning sign that allows you to sample them. Patient’s who are on tamoxifen who develop endometrial cancer frequently will present with postmenopausal spotting and when you work them up, they will have a well differentiated tumor and a very early cancer that is very treatable with hysterectomy or radiation, whatever the case may be. Therefore, it is felt that the benefits of tamoxifen therapy far outweigh the risks and therefore, though there is a seven time increased risk of developing endometrial cancer on tamoxifen, the overall risk for patient’s on tamoxifen is actually quite low.

Endometrial cancer is the most common cancer that you will see in your gynecologic practice. It is the most common malignancy that we see in the pelvis and it’s only second to breast cancer. It’s estimated that there will be between 30,000 to 40,000 cases in the new millennium diagnosed of endometrial cancer in the United States. If you are unfortunately enough to get a female cancer, endometrial cancer tends to be one of the friendlier cancers, although it has the highest incidence of malignancy in the female pelvis, it also has one of the lowest death rates due to it’s early detection rate which hopefully, as the talk goes on, we will understand why endometrial cancer, almost 75 to 85% of the time is picked up as stage I disease, where the other malignancies frequently are picked up as an advanced stage and therefore do not have the curable rate that endometrial cancer has. The median age of endometrial cancer is 61, the vast majority of cases occur between the ages of 50 and 59, this makes endometrial cancer a very easily detectable cancer because the vast majority of your women are postmenopausal. Indeed, 75% of patient’s diagnosed with endometrial cancer are post menopausal therefore they walk in with a big red flag saying I am having postmenopausal bleeding and this usually incites a very thorough workup and therefore early detection of the malignancy.
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Approximately 25% of women who are diagnosed with endometrial cancer unfortunately are not postmenopausal, and this group of patient’s is more difficult to diagnose, you really must listen to the patient’s history saying I am having increased menstrual bleeding during the month or I’m having heavier bleeding than I used to have and it takes an astute physician to say we really need to pursue this and get an endometrial biopsy. Approximately 5% of patient’s who develop endometrial cancer are below the age of 40, and again, this is even a more difficult group to diagnose. Of the group that is diagnosed before the age of 40, most of these patient’s are morbidly obese and have polycystic ovarian syndrome, so they do come walking in the door with a very enormous risk factor, you see this morbidly obese patient and you obtain a menstrual history, and say, maybe I ought to get a quick papular endometrial biopsy just to confirm that nothing further is going on.