e6-04: Cancer Prevention in Women

Overall, cancer is the second leading cause of mortality in women. Lung cancer is the most common reason for cancer death in women, followed by breast and colorectal cancers. Strategies for prevention and screening these and other preventable cancers are reviewed below.

Although lung cancer is not typically considered a "women's cancer," it is the leading cause of cancer mortality in both men and women. Primary prevention of lung cancer should be a high priority with encouragement of tobacco cessation among women who smoke, and screening recommendations for individuals at high risk for lung cancer are discussed in Chapters 1-08 and 39-09.

RISK FACTORS & RISK ASSESSMENT

Breast cancer is the most commonly detected non-skin cancer in women and the second leading cause of cancer death (see also Chapter 17-07). Breast cancer risk is increased with age and with a family history of breast cancer. Women who drink more than two alcoholic drinks per day are at increased risk for breast cancer, and exercise is associated with a decreased risk of breast cancer. Dietary intake has not been conclusively associated with breast cancer risk. Breast density is a risk factor for breast cancer; women with denser breasts as measured with mammography are at increased breast cancer risk. Although some states mandate that women with increased breast density on mammography be notified, it is not currently known what women can do to decrease this risk.

Various models have been used to predict a woman's risk for breast cancer. The National Cancer Institute has developed the Breast Cancer Risk Assessment Tool (http://www.cancer.gov/bcrisktool/), which is based on the Gail Model, a statistical model that uses the woman's own personal information to calculate a woman's risk of developing breast cancer in the next 5 years. Factors that are included are (1) the woman's age, (2) age at which she had her first menstrual period, (3) age at delivery of first live child, (4) number of first-degree relatives with breast cancer, (5) history of any breast biopsies, and (6) history of atypical hyperplasia. The outcome is a woman's 5-year risk of developing breast cancer compared with women of the same age and ethnicity. The model has been validated in white women and has been evaluated in black women and found to be relatively accurate, although it may underestimate the risk in black women with a history of previous breast biopsies. It has yet to be validated in women of other ethnicities. Women with a family history of breast, ovarian, tubal, or peritoneal cancer may need to be considered for genetic counseling, BRCA1 or BRCA2 testing, chemoprevention, or prophylactic surgery. The Gail model is less useful in women with an extensive family history of breast cancer (beyond first-degree relatives) and so other models have been proposed for use in these populations. These include the Ontario Family History Risk Assessment Tool, the Manchester Scoring System, the Referral Screening Tool, the Pedigree Assessment Tool, and the Family History Screen.

PRIMARY PREVENTION: CHEMOPREVENTION

In addition to lifestyle modifications, such as exercise and moderation of alcohol intake, chemoprevention of breast cancer is an option for some women. The selective estrogen receptor modifiers (SERMS) tamoxifen and raloxifene have both been shown to reduce invasive breast cancer rates in high-risk women. However, there are risks associated with SERM treatment. Tamoxifen is associated with an increased risk of endometrial cancer and deep venous thrombosis (DVT). Although raloxifene is not associated with an increased risk of endometrial cancer, the risk of DVT remains. Breast cancer risk increases with age, but the risk of adverse effects from chemoprevention does as well. Aromatase inhibitors, such as exemestane, show promise for breast cancer prevention but are not currently US Food and Drug Administration (FDA) approved for this indication. The United States Preventive Services Task Force (USPSTF) recommends that clinicians offer to prescribe risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, in women who are at increased risk for breast cancer and at low risk for adverse medication effects. Since the clinical trials of tamoxifen and raloxifene for breast cancer prevention used a 1.66% 5-year risk of breast cancer for decision making about initiation of therapy, this risk level is often used as a guide for medication treatment.

SECONDARY PREVENTION: BREAST CANCER SCREENING

Traditional breast cancer screening modalities include screening mammography, clinical breast examination, and breast self-examination. Breast cancer screening is discussed in detail in Chapters 1-08, 17-07, and 39-15 and in the references below.

Colorectal cancer is the third leading cause of cancer death in both men and women. In 2013, an estimated 9% of cancer deaths in women were caused by colorectal cancer. Since the risk of colorectal cancer increases with age, all women should be screened for colorectal cancer starting at the age of 50. Although the American Cancer Society now recommends beginning screening at the age of 45, this recommendation has not been universally accepted. The USPSTF recommends routine screening in men and women aged 50–75, individualized decision making about screening in individuals aged 76–85, and no screening after the age of 85. Details of the screening options and suggested screening intervals are described in Chapter 1-08.

Ovarian cancer is a relatively rare but dreaded cancer, with a lifetime incidence of about 1.2% in women with no family history of ovarian cancer. Because it is often detected late, treatment options may be limited.

Many of the risk factors for ovarian cancer such as age and family history are not modifiable, but there are protective factors, including having more than one full-term pregnancy, breast-feeding, and oral contraceptive use. Women at high risk for ovarian cancer, including women with a family history of ovarian cancer or a known familial cancer syndrome, should consider the use of oral contraceptives for as long as it is feasible.

Although screening for ovarian cancer with either the serum marker CA-125 or with transvaginal ultrasound is theoretically plausible, the rarity of the disease limits their use and leads to many false-positive test results (see also Chapter 18-17). The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, where women were screened for ovarian cancer with annual CA-125 and transvaginal ultrasound and monitored for 12.4 years, resulted in no reduction in ovarian cancer mortality. In addition, there were a large number of false-positive test results, some leading to surgical follow-up and resultant surgical complications. The United Kingdom Collaborative Trial of Ovarian Cancer Screening randomized over 200,000 women to screening with transvaginal ultrasound with or without CA-25 versus no screening. After a median follow-up of 11 years, there were no differences among groups in either ovarian cancer mortality or ovarian or primary peritoneal cancer mortality. The USPSTF does not recommend screening for ovarian cancer.