Gynecologic Cancer Prevention for Women At Risk for Malignancy (WARM)
Topics:
Introduction: Many American women are at increased risk for developing a cancer in the female reproductive tract organs. Fortunately, with adequate screening and, in certain cases, prophylactic surgery, the probability of developing a cancer can be minimized. The goal of this handout is to:
- Help identify which women are at increased risk for a gynecologic cancer and why.
- Outline an orderly plan of screening and prevention.
- Summarize the other cancer screening interventions from which these and all women would benefit.
Our goal is not to present a complete view of the medical literature, but to supply a practical and informative summary for our patients and other women at risk.
(back to topics)
Who is at increased risk? Women can be at an increased risk for developing one of the three most common cancers of the female reproductive organs (ovary, uterus, and cervix) because of numerous factors. In general, people are at an increased risk of developing a specific cancer because of three different phenomena:
- An inherited (genetic) predisposition.
- The occurrence of a certain malignancy that increases the risk of the developing another and different cancer.
- The effect of unique, life style choices.
Let's look at the three cancers listed above and address each of these three different phenomena and the roles that they play.
(back to topics)
Ovarian Cancer:
Inherited predisposition:
Between 5 and 15% of all cases of ovarian cancer develop as the end result of an inherited abnormality. These genetic abnormalities are numerous, with the most common being related to the BRCA 1 and 2 gene products. The corollary to this reality is that one can predict with a general degree of accuracy the probability that a woman will develop ovarian cancer based upon her family history. The average American woman has about a 1 in 70 chance of developing ovarian cancer if she lives to be 80 years. This is in comparison to a risk of 1 in 8 of breast cancer and 1 in 20 of colon cancer, should she live to the same age. A women with a proven BRCA 1 or 2 mutation has between a 30 and 45% chance (almost 1 in 2) of developing epithelial ovarian cancer (the type that develops from the surface of the ovary and is the most common cancer) in her lifetime. A woman who has two first-degree relatives that have proven epithelial ovarian cancer has about a one in seven chance of developing ovarian cancer. If a woman has one first-degree relative and two-second degree relatives (cousins, aunts, grandmothers) the risk of developing ovarian cancer is about one in twelve. It is evident that the fewer relatives that have ovarian cancer and the more distant they are, the less likely it is that a woman will develop the same disease. These numbers are also affected by background, with women of eastern European Jewish heritage (Ashkenzi) or at a higher risk. The age at which the family members developed ovarian cancer is also important: the younger a relative was when she developed ovarian cancer, the more likely that it was due to an inherited trait and the more likely that some other relative will develop ovarian cancer. One of the big problems with the issue of "inherited ovarian cancer" risk is getting, and keeping, the numbers straight! It is important to get the medical records of a relative who died from "ovarian cancer": many of these women never had ovarian cancer but had some other type of cancer. Similarly, it is important to constantly update your so-called "pedigree" or "family tree". Other family members age as you do. You may find that there are new cases of cancer that occur that may make a difference to your risk. The occurrence of other cancers that increase your risk: We know that women that have had any of the following cancers, particularly if these cancers occurred at a young age, are at an increased risk of developing ovarian cancer:
- breast cancer
- colon cancer
- endometrial cancer
Life Style related risk factors:
There are a wide range of life style activities or choices that increase and decrease a woman's risk of developing ovarian cancer: Those that increase the risk include:
- early onset of menstruation (menarche)
- late onset of menopause
- first term pregnancy after age 30 years
- few pregnancies
- not breast feeding or only breast feeding a new-born after age 30 years
- a history of infertility that was not due to a problem with ovulation (egg production)
- the use of high dose ovulation induction drugs for a long time period
Those events that decrease risk include:
- late menarche
- early menopause
- early first pregnancy
- multiple pregnancies
- use of the "Pill" (oral contraceptive tablet) for one year or more; the longer the use, the stronger the protective effect.
- breast feeding early and long
- prior hysterectomy/tubal ligation
A management protocol:
The first, and most important thing to do is get a handle on how much your risk of developing ovarian cancer is elevated. We strongly recommend to all patients that have any concern regarding this issue be evaluated by the Johns Hopkins Medical Institutions' Breast and Ovarian cancer Surveillance Service (BOSS) or a similar, high quality, dedicated service. During this evaluation a thorough family history is taken and an assessment of unique risks made. After this evaluation, patients return to The Kelly Service doctors for a further discussion. Basically one of three decisions can be made:
- The patient is not at a significant increase in risk for developing ovarian cancer. Therefore, focussed screening (anything more than annual pelvic examinations) is not warranted.
- The patient is at an increased risk for the development of ovarian cancer and therefore a candidate for focussed screening (annual vaginal probe ultrasound with color-flow Doppler and ovarian volume assessment and CA-125) in addition to routine screening techniques (a focussed history and review of symptoms and an abdominal/pelvic examination).
- The patient is at such a high increased risk of developing ovarian cancer that we would recommend that she under go a prophylactic oophorectomy (removal of the ovary before cancer can develop).
Ovarian Cancer Screening:
It is important that the patient not be deceived regarding the merits of screening for ovarian cancer. It has only been in the last few years that there has been enough high quality data to support screening in WARM. Unfortunately, screening is not perfect, and just like with mammograms and Pap smears, not all pre-cancer conditions or early cancers are detected. Furthermore, some more advanced cancers will still occur. The present standard for ovarian cancer screening consists of a transvaginal ultrasound looking for very specific findings. It is remarkably important that this ultrasound be of the highest quality possible, as so much is at stake if small changes are missed. The ultrasound needs to be done on a yearly basis until a women has either undergone prophylactic oophorectomy or has lived into her 8th decade of life. There is no value in doing blood testings looking at so called "tumor markers" as none of these have proven to be accurate enough to justify the cost. However, there probably is a value in following the "trends" in the levels of tumor markers.
Prophylactic Oophorectomy:
There are two significant controversies that surround the use of prophylactic oophorectomy and its role in the prevention of ovarian cancer in women that are at increased risk of developing ovarian cancer. These controversies are: 1) who is at such high risk that the procedure can be justified and 2) when should it be performed. There are no "cast in stone" answers to either of these questions. However we generally feel that individuals who have a risk of developing ovarian cancer that is higher than the risk of removing the ovaries ( those with two first degree relatives or two second degree and one first degree relative, or with few relatives but personal high risk criteria such as early breast cancer, never having a baby, etc.) should be offered this procedure. Prophylactic oophorectomy in most instances can be done using the laparoscope, avoiding large abdominal incisions, with the patient going home the day of surgery or the next morning. If the uterus is normal and the patient has no history of endometrial or cervical pre-cancers, we would encourage that it not be removed. If there is a justification for a hysterectomy, our preference is to perform a laparoscopically assisted vaginal hysterectomy, a procedure that has a much shorter recovery time than the conventional abdominal hysterectomy (the one that requires a large abdominal incision). Then the question is "when". Generally, the ovaries should be removed a decade before the youngest known relative developed ovarian cancer or at the completion of child bearing, which ever comes first. Removing the ovaries possess complex issues regarding hormone replacement therapy. These issues are summarized in another patient handout that The Kelly Service physicians have developed and would be happy to give you. We are concerned that in very young women who have a questionable risk of developing ovarian cancer, the negative effects of lack of female hormones for a long time out weigh any potential benefits of removing the ovaries early. This illustration emphasizes the need to have an open and thorough one on one discussion with your doctor regarding these issues.
(back to topics)
Endometrial Cancer:
Inherited Predisposition:
Only a small percentage (approximately 5%) of women who develop this, the most common of gynecologic cancers, have a genetic predisposition. Because this cancer is most likely to be diagnosed early and is relatively easily treated, the impact of this inherited predilection is less than in ovarian cancer.
Occurrence of other cancers that increase your risk:
A history of ovarian, colon or breast cancer increases the risk of developing endometrial cancer. Most of this increase in risk is not due to a genetic predisposition, but a commonality in other, predisposing factors. The relationship of breast cancer to increased risk of endometrial cancer is one that, simply as a result of the number of women in the United States who develop cancer, is an important one. A women that has had breast cancer has a doubling of her life time risk of developing endometrial cancer; if she takes Tamoxifen the risk is doubled again. (See section on predisposing factors below).
Life Style Related Risk Factors:
The majority of endometrial cancers have, as a cofactor at least, the presence of an estrogen rich, progesterone deficient hormonal environment. There are numerous causes for this environment:
- Exogenous estrogen (tablets, including Tamoxifen, creams, patches, food sources, etc.) that is either not or inadequately blocked by progesterone.
- Excessive endogenous estrogen in relationship to the amount of progesterone produced. This is most commonly due to the patient being overweight. The more overweight a woman is, the more likely that she will develop endometrial cancer. Other causes for excess endogenous estrogen are the fact that the woman doesn't ovulate (evident as menstruate) regularly (once every 45-60 days, consistently) or the presence of a very rare type of ovarian cancer (Granulosa Thecal Cell Tumors).
- Medical Problems such as sugar diabetes and hypertension increase the risk of women developing endometrial cancer.
- A history of prior pelvic radiation.
Those life events that decrease the risk of developing endometiral cancer include:
- regular menses
- multiple pregnancies
- late onset of menses and early onset of menopause
- use of birth control pills
Screening for endometrial cancer:
Recent data has demonstrated that there is no value in doing routine screening with either ultrasounds or endometrial biopsies on women that are at increased risk of developing endometrial cancer. The reason is that the disease is very likely to be symptomatic early and relatively easily cured therefore decreasing the need for screening using expensive tools. However it must be stated that the threshold for performing endometrial evaluations (ultrasounds and biopsies) must be at ground level for women with postmenopausal bleeding or pre-menopausal bleeding having any of the above associated risk factors.
Prophylactic Hysterectomy:
There is no role for the performance of prophylactic hysterectomy in the totally asymptotic patient devoid of symptoms with a normal uterus. However, if women have other indications for a hysterectomy, the procedure can be justified.
(back to topics)
Cervical Cancer:
Genetic Predisposition:
Recent investigations have demonstrated that certain ethnic groups (those of Native American ancestry) are more likely to develop cervical cancer than other ethnic groups. However, this should not be considered as a specific genetic predisposition, as what happens in ovarian cancer and BRCA 1, but a general susceptibility. There has not been identified any specific unique genetic pre-dispositions for cervical cancer.
Occurrence of other cancers that increase your risk:
The other cancers that occur in the lower genital tract as a result of infection with the Human Papilloma Virus (HPV) (vaginal, vulvar, and peri-anal cancers) all increase the risk of a women developing cervical cancer. It is more likely, however, that cervical cancer will be the first of the HPV cancers to occur and therefore it is uncommon that a women will have one of the other cancers listed above and then develop cervical cancer.
Life Style Related Risk Factors: The risk factors for developing cervical cancer have been well described and identified. They are the same as those related to the development of cervical dysplasias (pre-cancers) and include:
- young age at first intercourse
- a short time period from the beginning of menstruation and the beginning of vaginal intercourse
- multiple sexual partners, particularly at a young age
- history of having genital warts
- cigarette smoking
- having a sexual partner who has had multiple sexual partners
- history of an abnormal Pap smear
- no prior Pap smear screening
Those behaviors that would be protective, of course, are the opposites of what is listed above.
Screening for Cervical Cancer:
Screening for cervical cancer is really based on screening for the pre cancers. This is done with the Pap smear, the greatest success story in the history of cancer screening and prevention. Pap smear screening has decreased the mortality from cervical cancer over 70% over the last 5 decades in countries where it is widely used. Sadly, many women are either inadequately or never screened. In fact, between 50 and 60 % of the women who die of cervical cancer have had inadequate or no screening !! Women need to be screened beginning at the time of onset of vaginal intercourse or at age 18, which ever comes first. Thereafter, women should be screened on a once a year basis until three negative Pap smears have been taken AND the patient is in a monogamous (both partners) and stable sexual relationship. If there is any change (for example a new sexual partner), it is recommended that the women go back to every year screening until three more normal Paps smears have been collected.
Prophylactic Surgery:
There is no role for prophylactic surgery, specifically hysterectomy, in the prevention of cervical cancer. In fact we find that there is a tendency in the United States to actually over treat patients who really don't need it !! Treatment should be very specific and focussed on a biopsy proven finding of a pre-cancer or cancerous change.
(back to topics)
Other Cancers that should be screened for: It is very important that women continue they're screening for the two, big, non-smoking related cancers: Breast and Colon. Each of these cancers effects more US women per year than all the Gynecologic Cancers combined. Despite this fact, many American women are hesitant to get the screening they need.
Breast Cancer: Breast cancer screening is a combination of: Breast Self-Examination (BSE), health care provider performed breast examination, and mammograms, with the timing of the first radiographic screening based upon the risk of disease occurrence. Unquestionably, yearly mammographic screening should start by age 50 years.
Colon Cancer: This screening is a combination of digital rectal examination with stool blood testing and sigmoidoscopy or colonoscopy. Digital examinations should be done with the annual pelvic examination. Colonoscopy is usually first performed when a women reach age 50 years and is done on a schedule based upon risk for developing colo-rectal cancer and findings on colonoscopy. There are some individuals who are at risk of developing colo-rectal cancer at a younger age; these people need to start their screening earlier. Your primary care physician can tell you whether or not you would benefit from early colonoscopy.
(back to topics)
Summary: Most women are not at significant increased risk for the occurrence of a gynecologic malignancy. The determination as to whether one is or not can usually be made by a careful history (including family) and physical examination. Fortunately, even those women who are at increased risk can usually have disease diagnosed early and treated successfully thanks to the wide availability of screening tools.
(back to topics)
|
|
