Gynecologic care of the cancer patient
As more Ob/Gyns provide follow-up care to patients who have survived cancer, there is an increased need for information on how to better care for these women with regard to menopause, risk for subsequent disease, and preventive care.
- Selective serotonin reuptake inhibitors (SSRIs), clonidine hydrochloride, and megestrol alleviate hot flushes in women who opt not to take hormone replacement therapy (HRT) due to concerns about subsequent disease.
- Local estrogen therapy in the form of an estradiol-releasing vaginal tablet or ring effectively improves vaginal atrophy and has a higher patient acceptability than vaginal cream.
- Because a majority of women who have survived breast cancer have not been screened for BRCA1 and BRCA2 mutations, Ob/Gyns should screen survivors to identify those patients at risk for subsequent disease.
- Approximately half of the women who survive breast or a gynecologic cancer report severe, long-lasting sexual problems.
As more is discovered about cancer, caring for the cancer patient has become even more complicated. Women who have survived cancer, even nongynecologic diseases, increasingly are being followed by general obstetrician/gynecologists or primary care physicians. To help Ob/Gyns provide better care, this review will summarize cancer patients’ special needs with regard to menopause and premature menopause, genetic screening techniques, and well-woman care.
Only about 15% of postmenopausal women use HRT.
In evaluating the needs of the cancer patient, an understanding of the type of cancer and the surgical and medical management the woman has undergone is key. This knowledge aids the management of sexual health, fertility, and menopause. Additionally, depending on the type of cancer she has had, the patient may be exposed to health risks not previously identified. In these cases, an understanding of the familial basis of some cancers and hereditary syndromes is essential, as it can help identify those who may be at risk for subsequent malignancies or conditions.
Finally, as with all well-woman care, preventive measures such as bone densitometry, mammography, colonoscopy, exercise, self-breast examination, and smoking cessation must be addressed and discussed.
Many young women with a cancer diagnosis face premature menopause. In addition to the psychological issues stemming from premature ovarian failure such as those related to fertility, these women experience many of the typical menopausal symptoms and other health risks well before their healthy counterparts.
In the decades since hormone replacement therapy (HRT) was introduced, there has been increasing controversy and confusion among patients and physicians about its benefits and risks. In particular, because of the possible role of estrogen in the pathogenesis of breast cancer, its use for post-menopausal therapy has been challenged.1-3
Currently, only about 15% of post-menopausal women use HRT, in part due to the concerns about breast cancer. Other reasons include breast engorgement and tenderness and a resumption of vaginal bleeding.
Most health-care providers believe HRT is contraindicated for breast cancer survivors. However, withholding HRT from all postmenopausal women would be a disservice to many, as it would expose them to health risks that would outweigh the risk for breast cancer. One of the clinician’s roles is to identify patients who would benefit from HRT and to avoid exposing others to unreasonable risk. Fortunately, the available alternatives to HRT are rapidly increasing in response to the demand this controversy has generated.
BRCA 1 and BRCA 2 are responsible for most inherited ovarian carcinomas.
Hormone replacement therapy initially was intended for short-term use in the management of vasomotor symptoms. The health benefits that were subsequently identified supported a longer duration of use.4,5 These include improving hot flushes, protecting bone density, and combating urogenital atrophy, but more recently, the potential benefit that hormones may have on cardiac health has come under scrutiny.6-8
Vasomotor symptoms. Menopausal women often complain of debilitating vasomotor flushes. For women who take tamoxifen, e.g., those with a history of breast cancer, vasomotor symptoms may be potentiated.9,10 Traditional HRT regimens, either oral or transdermal, have been effective in treating vasomotor symptoms in 85% to 90% of women.11 Even so, increasing numbers of women are turning to an ever-growing array of nonestrogen agents in an effort to alleviate symptoms and minimize their perceived risk of breast cancer.
Agents that can be used to alleviate hot flushes include selective serotonin reuptake inhibitors (SSRIs) such as venlafaxine hydrochloride in small doses, e.g., 25 to 75 mg daily.12,13 Clonidine hydrochloride, an antihypertensive, also is effective, but its side effects limit its use.14 If the 0.1-mg patch is used, it should be changed weekly, and if the drug is administered orally, the dosage should not exceed 0.1 mg twice daily. Megestrol, a progestin, also has been shown to be effective.15
Recently, phytoestrogens have been sought as substitutes for traditional HRT. While there is some evidence they may improve vasomotor flushes and protect against bone cancer and cardiovascular disease, results have been inconsistent and definitive studies are lacking.16-21
It is beyond the scope of this article to delineate or evaluate the many herbal and nutritional supplements available for the management of vasomotor symptoms. According to the literature, their efficacy is questionable. Nonetheless, the industries that promote these products are among the fastest-growing businesses, largely due to the public’s fears about breast cancer.
Genitourinary symptoms. Atrophic changes of the vagina are common in the menopausal years and are associated with generalized pruritus and dyspareunia to variable degrees in each individual. This, in addition to the cancer diagnosis and treatment, can lead to symptoms of depression, low self-esteem, and relationship issues surrounding sexuality. It is essential to address symptoms of vaginal atrophy and discuss treatment options with the cancer patient. Local estrogen therapy in the form of a 17-beta estradiol-releasing ring or tablet is an effective method22,23 and has been used successfully in breast cancer survivors at our institution. Since the absorption of estrogen is minimal, it is thought to be safe.24 Further, the risk of endometrial cancer associated with the use of unopposed estrogen is lower with the vaginal ring or tablet than with estrogen cream, as evidenced by endometrial biopsies (TABLE 1).22 In addition, it appears patient satisfaction and acceptability, i.e., ease and comfort of administration, is greater with the tablet than with the cream (Figure 1).
FIGURE 1 Patient satisfaction with vaginal tablets and cream
Source: Rioux JE, Devlin C, Gelfrand M, et al. 17-beta estradiol vaginal tablet versus conjugated equine estrogen cream to relieve menopausal atrophic vaginitis. Menopause. 2000;7:156-161.TABLE 1
Safety of vaginal tablets versus cream for the treatment of atrophic vaginitis
VAGINAL TABLETS (N=80)
VAGINAL CREAM (N=79)
Patients with biopsies/stained biopsies
Weakly proliferative endometrium
Biopsies with insufficient tissue
Source: Rioux JE, Devlin C, Gelfrand M, et al. 17-beta estradiol vaginal tablet versus conjugated equine estrogen cream to relieve menopausal atrophic vaginitis. Menopause. 2000;7:156-161.
Screening for genetic mutations
Genetic counseling should be offered to all patients who appear to carry an increased cancer risk based on their personal or family histories. Unfortunately, many women with a history of breast or ovarian cancer have never been offered such counseling. Therefore, it is important for Ob/Gyns to screen cancer survivors to identify those patients at risk for subsequent disease.
Although most cancers arise from somatic mutations acquired after birth, approximately 10% of both breast and ovarian cancers are thought to result from inherited gene mutations that are passed down through the maternal or paternal lines. The theory that some breast and ovarian cancers have a genetic basis has been entertained for decades, but only recently have the gene mutations BRCA1 and BRCA2 been identified.25,26 Approximately 85% of hereditary breast carcinomas result from alterations in the BRCA1 and BRCA2 genes.27 These genes also are responsible for most inherited ovarian carcinomas.
Studies also have shown that in families with a history of ovarian cancer or early-onset breast cancer, the risk of developing breast cancer by age 70 is more than 80% for women with BRCA1 or BRCA2 mutations.26,28-30 The risk of developing breast cancer before the age of 50 is 33% to 50% in women with a gene mutation in BRCA1 or BRCA2, versus only 2% in a woman without a gene mutation.30,31
The risk of ovarian cancer conferred by mutations in BRCA1 appears to be greater than that for BRCA2. The BRCA1 mutation is associated with a risk of ovarian cancer between 28% and 44% by age 70, as compared to 1.8% in the general population.28,30,32 The BRCA2-associated risk of ovarian cancer is estimated at 27%, with most cases occurring after the age of 50. TABLE 2 summarizes the risk of cancer conferred by inherited mutations in BRCA1 and BRCA2.
Three forms of hereditary epithelial ovarian cancer exist.26,28,33,34 The most common form appears as a component of the hereditary breast/ovarian cancer syndrome. In these families, multiple cases of breast and ovarian cancer are found, and mutations in the BRCA1 gene are thought to account for the vast majority of them.
The second form of hereditary ovarian cancer occurs as site-specific cancer and is inherited as an autosomal-dominant trait. Mutations in BRCA1 also account for a large proportion of these cases. The third form of hereditary ovarian cancer occurs as a component of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. It is characterized by an autosomal-dominant transmission of nonpolyposis colon cancer along with adenocarcinomas of the ovary, uterus, breast, kidney, stomach, pancreas, small bowel, and biliary tree.35
The hallmark of hereditary ovarian cancers is their occurrence at a younger age, the mean being in the mid-40s, with 17% occurring by age 40.36 Therefore, if prophylactic surgery is considered, it generally should be performed prior to the end of the fourth decade of life, after the patient has completed child-bearing. However, since some cases of hereditary ovarian cancer occur in later life, it is thought that even a woman in her 60s or 70s may benefit from prophylactic surgery. Patients undergoing the surgery should be counseled that while their risk is reduced significantly, it is not eliminated. Primary peritoneal carcinomatosis remains a possibility; this risk is estimated at 2% to 11% for women who have undergone prophylactic surgery. 37,38
Oral contraceptives (OCs) have been evaluated for their possible role in the prevention of ovarian cancer in the general and high-risk populations. It is estimated that OC use may reduce the risk of hereditary ovarian cancer by as much as 60%.39 However, the benefits of this therapy need to be weighed against the possible increased risk of breast cancer in patients with BRCA1 and BRCA2 mutations.40,41
Due to the low sensitivity and specificity of available screening tests and the relatively low prevalence of ovarian cancer in the general population, routine screening is not recommended, except in women who are at increased risk. Such high-risk women include those who have a personal or family history of ovarian or breast cancer, known mutations in the BRCA1 and BRCA2 genes, or who are of Ashkenazi Jewish descent with personal or family histories of breast or ovarian cancer or both.
No single screening modality has been proven effective. Studies evaluating the role of semiannual pelvic examinations in conjunction with transvaginal sonography (TVS) and CA125 evaluations are under way.42 These modalities currently are the best options in the high-risk population.43-45
For the patient identified as having HNPCC syndrome, screening should include annual endometrial biopsies, breast cancer screening, ovarian cancer screening (as above), colonoscopy, and urine cytology. Prophylactic hysterectomy and oophorectomy may be considered to reduce the gynecologic cancer risks.46
TABLE 3 summarizes surveillance options for women at high risk for familial cancers. Since screening options are limited in sensitivity and specificity, the guidelines are based on expert opinion rather than randomized studies.47
Cancer risk conferred by inherited mutations in BRCA1 and BRCA2
Up to 87% by age 70; 33% to 50% by age 50
BRCA1 or BRCA2
Risk of contralateral breast cancer, 64% by age 70; 25% within 5 years
28% to 44% by age 70 to 80
27% by age 70 10-fold increased risk following breast cancer
3.3-fold increased risk
Source: Frank TS. Hereditary risk of breast and ovarian carcinoma: the role of the oncologist. Oncologist. 1998;3:403-412