Breast Cancer: Rates, Risk Factors,
Prevention and Screening

Introduction

Breast cancer is the leading and most common cancer in American women, accounting for 192,200 new cases, or 31% of all cancers in women. It accounts for 15% of all cancer deaths in women; 40,200 deaths from breast cancer were projected for 2001. The number of women diagnosed with breast cancer generally remained level during the 1990s, but may be decreasing in younger women. The number of women dying from breast cancer has also declined. White women are more likely to develop breast cancer than are women of other racial and ethnic groups, but African American women are more likely to die of this disease. Recent statistics clearly point out that if breast cancer is found early, five-year survival rates can approach 97%. Improved survival may be attributed to national efforts to encourage women to practice breast self-examination and to have regular mammograms and clinical breast exams by their health care providers.

Risk Factors

Risk factor assessment and risk reduction counseling are essential to promoting primary and secondary prevention of breast cancer. To assure effective assessment and counseling, a thorough understanding of specific risk factors is necessary. In general women have a 12% (1 in 8) lifetime risk of developing breast cancer. An individual’s risk may increase or decrease, depending on the presence of factors that affect this overall risk. Risk factors may be divided into two categories: modifiable (those we can do something about) and non-modifiable.

Non-modifiable Risk Factors

Age: Increasing age is a significant risk factor. Over three-quarters of all breast cancers occur in women over age fifty. The probability of developing invasive breast cancer before the age of 40 is 1 in 235. Between ages 40 and 59 it is 1 in 25 and between ages 60 and 79 it is 1 in 15.

Gender: Women are nearly 100 times more likely to develop breast cancer than men. This gender difference is linked to hormonal influences.

Race: New cases of breast cancer occur most commonly in white women (114/100,000), followed closely by black women (100/100,000). Asian/Pacific Islander, Hispanic and American Indian women have a much lower risk (75, 69 and 33/100,000, respectively).

Genetics: Five to ten percent of all breast cancers may be attributed to inherited gene mutation(s). The BRCA1 and BRCA2 cancer susceptibility genes are responsible for about 50% of all hereditary breast cancer cases and about 80% of all breast and ovarian cancer cases that are inherited. Genetic mutations are most often found in families with early onset breast cancer (before the age of 50), bilateral breast cancer, both breast and ovarian cancer, or multiple breast cancer cases. Women with a BRCA1 or BRCA2 mutation have up to an 85% lifetime risk of developing breast cancer, and each offspring (male or female) has a 50% chance of inheriting the mutation due to autosomal dominant transmission. Women with a BRCA1 or BRCA2 mutation are also at increased risk for ovarian cancer. A small number of cases of hereditary breast cancer may be attributed to rare genetic cancer predispositions, including Li-Fraumeni syndrome(TP53 gene) and Cowden (PTEN gene) syndrome.

Family History: Approximately 15-20% of all breast cancers are related to a family history of breast cancer but without evidence of strong genetic linkage through autosomal dominant transmission. In these family clusters, breast cancer may occur due to a variety of factors including a weaker genetic predisposition, lifestyle practices and/or environmental factors. The degree of risk varies by the type and number for relatives effected. A woman with a positive family history in one first-degree relative (mother, sister, daughter) doubles her breast cancer risk. A positive family history in a second-degree relative (aunt, grandmother) increases her risk by only 50%, while a positive family history in two first-degree relatives increases her risk five-fold. It is very important to understand that familial breast cancer risk can come from either maternal or paternal relatives.

Personal history: A previous personal history of breast cancer increases the risk of developing breast cancer in the opposite breast by three to four-fold.

Previous breast biopsies: A breast biopsy revealing atypical hyperplasia increases breast cancer risk by at least four-fold, while those showing proliferative changes without atypia increase risk by only 50 to 100%. Finally, simply having had one or more breast biopsies, regardless of the histologic findings, can increase breast cancer risk by approximately 50%.

Previous chest radiation: Women with a history of chest radiation therapy for treatment of cancers such as Hodgkin’s disease or non-Hodgkin’s lymphoma face a two to four-fold increased risk.

Hormonal influences: The impact of estrogen on breast cancer risk has been evaluated extensively and continues to be controversial. It is clear that both endogenous and exogenous estrogen (and progesterone) promote proliferation of breast epithelium, or tissue. This increased activity can result in greater levels of DNA damage, which may have an effect on carcinogenesis (cancer development). This process supports the hypothesis that the longer breast tissue is exposed to estrogen, the greater the carcinogenic impact. Two non-modifiable risk factors associated with this hormonal influence are: a) menarche before the age of twelve increases breast cancer risk by approximately 20% and b) menopause occurring after the age of fifty-five doubles breast cancer risk.

Modifiable Risk Factors

Hormonal Influences: The following risk factors have a hormonal basis and, to some degree, may be influenced by personal action.

Pregnancy: When the menstrual cycle is interrupted, particularly at an early age, breast cancer risk is reduced. Pregnancy before the age of twenty decreases breast cancer risk by about 20%, while pregnancy after thirty or nulliparity (never being pregnant) slightly increases risk. Generally, the greater the number of full-term pregnancies, the lower the risk of breast cancer.

Lactation: Because breast-feeding decreases the number of menstrual cycles, breast cancer risk may be decreased slightly, particularly for women who breast-feed for at least 1.5 to 2 years.

Oophorectomy: Early menopause caused by prophylactic oophorectomy (preventive removal of the ovaries) has been shown to decrease breast cancer risk in some women.

Oral contraceptive (OC) use: There is only a small increase in breast cancer risk with OC use, and it returns to normal ten years after OCs are discontinued.

Hormone Replacement Therapy (HRT): HRT (including both estrogen only or estrogen and progestin replacement therapy) may annually increase breast cancer risk by about 2% for each year of use. Long-term use (over 10 years) of HRT may increase risk by 30-40%. Risk decreases after discontinuing use and returns to that of the general population five years after stopping therapy. Additionally, risk associated with HRT is similar for women with and without a family history of breast cancer. There are benefits to taking HRT, including improved lipid profile and decreased osteoporosis; therefore, women should talk with their health care provider before making a decision about therapy. Finally, women taking both estrogen and progesterone (HRT) face a slightly greater risk than women taking estrogen only, as progesterone can increase breast cell proliferation.

Diet: Although epidemiologic data have supported the hypothesis that reduced fat intake may decrease breast cancer incidence, many cohort studies have not found a significant association. The Nurses’ Health Study, supported by findings from smaller cohort studies, noted that a low fat but high carbohydrate diet was associated with a slight increase in breast cancer risk. The Women’s Health Initiative, a randomized placebo-control primary prevention trial of over 47,000 women, is currently investigating the impact of diet on breast cancer risk. Results are expected in five years.

Body Weight: Obesity, particularly weight gain from early adulthood to the postmenopausal period, is associated with an approximate 60% to 100% increase in breast cancer incidence, especially in women not taking HRT. This is most likely due to the increased production of endogenous estrogen in this population.

Vitamins: Vitamin A has shown a modest protective effect relative to breast cancer. No beneficial association has been demonstrated for vitamins C or E or selenium.

Phytoestrogens: The effects of phytoestrogen, nutrients found in soy products such as tofu or tempeh, on breast cancer risk is controversial. Some studies suggest that soy taken during midlife, when endogenous estrogen levels are lower, may increase estrogen levels and thus increase breast cell proliferation.

Exercise: Regular exercise seems to be associated with a decrease in breast cancer risk by about 20% to 50%, especially among women who have maintained normal weight during adulthood.

Alcohol: Although results from studies vary, breast cancer risk seems to increase as alcohol intake increases. Consuming one drink per day increases risk by about 10% to 20%, while 2-5 drinks per day may result in a 40% to 50% increase.

Smoking: Case-control studies have found a positive association between smoking and breast cancer, and a Canadian study found a more than 200% increase in risk of premenopausal breast cancer in women exposed to either active or passive smoking.

Environmental Factors: Environmental pollutants such as pesticides and polychlorinated biphenyls (PCBs) have been implicated in breast cancer development, although research remains inconclusive.

Screening

The goal of screening is to decrease the number of deaths by detecting breast cancer early, when treatment is most effective and long-term survival greatest. The American Cancer Society recommends the following strategies for women.

Recommendations for women at average risk

·Monthly breast self-examinations beginning at age 20.

·Clinical breast examination performed by a health care provider every three years between age 20 to 30 and then yearly beginning at 40.

·Annual mammography beginning at age 40.

Recommendations for women at increased risk

Screening guidelines for carriers of a BRCA1 or BRCA2 gene mutation, or women at risk for being a mutation carrier based on a strong family history, require earlier and more frequent surveillance intervals.

·Monthly breast self-examinations should begin by age 18.

·Clinical breast examination should begin at age 25 to 35 and be performed once or twice a year.

·Yearly mammograms should begin at age 25 to 35 or, if applicable, 10 years before the age of the youngest affected family member.

Primary Prevention

Controlling modifiable risk factors by adopting a healthy diet and life-style are important and basic to reducing the risk of breast and other cancers. Recommendations include a low-fat diet high in fruits and vegetables, avoidance of cigarettes and alcohol, or limiting alcohol intake to two or three drinks per week. Regular exercise and maintenance of normal weight are also key factors.

For women at increased risk for developing breast cancer, chemoprevention and prophylactic mastectomy are options to consider. Tamoxifen (Nolvadex), a selective estrogen receptor modulator (SERM), can decrease breast cancer risk by approximately 50% by blocking the effects of estrogen on breast tissue. The decision to start Tamoxifen should be carefully analyzed by the patient and their health care provider as Tamoxifen has been shown to increase the risk of endometrial cancer, pulmonary embolism, deep vein thrombosis, stroke and cataracts, particularly in women fifty and older. Raloxifene, another SERM, is currently approved only for the treatment of osteoporosis in postmenopausal women, but may also decrease the incidence of breast cancer with less endometrial cancer risk. Currently, the Study of Tamoxifen and Raloxifene (STAR) trial, a randomized double-blind study, is evaluating the effectiveness of Tamoxifen and Raloxifene, but results will not be available for several years. Finally, for women facing a significant breast cancer risk, prophylactic mastectomy (preventive removal of the breasts) has been shown to decrease risk by 90%. However, the potential psychological consequences must be carefully considered.

Research efforts will continue to clarify the role of specific risk factors on breast cancer development and the effectiveness of both current and evolving screening and prevention strategies.Careful individualized risk assessment and counseling will continue to play a key role in reducing breast cancer rates and promoting early detection.

References

Alberg, A.J., Singh, S., May, J.W., and Helzlsouer, K.J. (2000). Epidemiology, prevention and early detection of breast cancer.Current Opinion in Oncology, 12 515-520.

American Society of Clinical Oncologists. 1998. ASCO Curriculum.

American Cancer Society, 2001 Cancer Facts and Figures 2001. ACS Web site.

Vogel, V.G. (2000). Breast cancer prevention: A review of current evidence. CA-A Cancer Journal for Clinicians,50(3), 156-169.

Willett, W. C. (2001). Diet and Breast Cancer. Journal of Internal Medicine 249; 395-411.

Susan Appling, MSN, CRNP