miércoles, 1 de mayo de 2019

Breast Cancer Prevention (PDQ®) 3/4 —Health Professional Version - National Cancer Institute

Breast Cancer Prevention (PDQ®)—Health Professional Version - National Cancer Institute

National Cancer Institute

Breast Cancer Prevention (PDQ®)–Health Professional Version


Prophylactic mastectomy

A retrospective cohort study evaluated the impact of bilateral prophylactic mastectomy on breast cancer incidence among women at high and moderate risk on the basis of family history.[120] BRCA mutation status was not known. Subcutaneous, rather than total, mastectomy was performed in 90% of these women. After a median follow-up of 14 years postsurgery, the risk reduction for the 425 moderate-risk women was 89%; for the 214 high-risk women, it was 90% to 94%, depending on the method used to calculate expected rates of breast cancer. The risk reduction for breast cancer mortality was 100% for moderate-risk women and 81% for high-risk women. Because the study used family history as a risk indicator rather than genetic testing, breast cancer risk may be overestimated.
The rate of bilateral mastectomy among women with unilateral disease (DCIS and early-stage invasive breast cancer) was reported to have increased from 1.9% in 1998 to 11.2% in 2011 based on data from the U.S. National Cancer Data Base.[121]
No studies have been done on the benefits of prophylactic mastectomy in the average-risk population to prevent contralateral breast cancer in women with an ipsilateral breast cancer.

Prophylactic oophorectomy

Ovarian ablation and oophorectomy are associated with decreased breast cancer risk in normal women and in women with increased risk resulting from thoracic irradiation. (Refer to the Endogenous estrogen section in the Description of the Evidence section of this summary for more information.) Observational studies of women with high breast cancer risk resulting from BRCA1 or BRCA2 gene mutations showed that prophylactic oophorectomy to prevent ovarian cancer was also associated with a 50% decrease in breast cancer incidence.[122-124] These studies are confounded by selection bias, family relationships between patients and controls, indications for oophorectomy, and inadequate information about hormone use. A prospective cohort study had similar findings, with a greater breast cancer risk reduction in BRCA2 mutation carriers than in BRCA1 carriers.[125]

Factors and Interventions With Inadequate Evidence of an Association

Hormonal contraceptives

Oral contraceptives have been associated with a small increased risk of breast cancer in current users that diminishes over time.[126] A well-conducted case-control study did not observe an association between breast cancer risk and oral contraceptive use for every use, duration of use, or recency of use.[127]
Another case-control study found no increased risk of breast cancer associated with the use of injectable or implantable progestin-only contraceptives in women aged 35 to 64 years.[128]
A nationwide prospective cohort study in Denmark found that women who currently or recently used contemporary hormonal contraceptives had a higher risk of breast cancer than did women who had never used hormonal contraceptives. Moreover, the risk of breast cancer increased with longer duration of hormonal contraceptive use. However, in absolute terms, the effect of oral contraceptives on breast cancer risk was very small. Thus, approximately one extra case of breast cancer would be expected for every 7,690 women using hormonal contraception for 1 year.[129]

Environmental factors

Occupational, environmental, or chemical exposures have been proposed as causes of breast cancer. Although some findings suggest that organochlorine exposures, such as those associated with insecticides, might be associated with an increase in breast cancer risk,[130,131] other case-control and nested case-control studies do not.[132-137] Studies reporting positive associations have been inconsistent in the identification of responsible organochlorines. Some of these substances have weak estrogenic effects, but their effect on breast cancer risk remains unproven. The use of dichloro-diphenyl-trichloroethane was banned in the United States in 1972, and the production of polychlorinated biphenyls was stopped in 1977.

Factors and Interventions With Adequate Evidence of Little or No Association

Abortion

Abortion has been proposed as a risk factor for breast cancer. Findings from observational studies have varied; some studies showed an association, while other studies did not. Observational studies that support this association were less rigorous and potentially biased because of differential recall by women on a socially sensitive issue.[138-141] For example, the impact of recall or reporting bias was demonstrated in a study that compared regions with different social attitudes on abortion.[142] The Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists has concluded that “more rigorous recent studies demonstrate no causal relationship between induced abortion and a subsequent increase in breast cancer risk.”[143] Studies that used prospectively recorded data regarding abortion, thereby avoiding recall bias, largely showed no association with the subsequent development of breast cancer.[144-149]

Diet

Any effect of dietary modifications on breast cancer would likely depend on the type of modification. However, there is little evidence that dietary modifications of any kind have an impact on the incidence of breast cancer.
There are very few randomized trials in humans comparing cancer incidence for different diets. Most studies are observational—including post hoc analyses of randomized trials—and are subject to biases that may be so large as to render the observation difficult to interpret. In particular, p-values and CIs do not have the same interpretation as when calculated for the primary endpoint in a randomized trial.
A summary of ecological studies published before 1975 showed a positive correlation between international age-adjusted breast cancer mortality rates and the estimated per capita consumption of dietary fat.[150] Results of case-control studies have been mixed. Twenty years later, a pooled analysis of results from seven cohort studies found no association between total dietary fat intake and breast cancer risk.[151]
A randomized, controlled, dietary modification study was undertaken among 48,835 postmenopausal women aged 50 to 79 years who were also enrolled in the WHI. The intervention promoted a goal of reducing total fat intake by 20% by increasing vegetable, fruit, and grain consumption. The intervention group reduced fat intake by approximately 10% for more than 8.1 years of follow-up, resulting in lower estradiol and gamma-tocopherol levels, but no persistent weight loss. The incidence of invasive breast cancer was numerically, but not statistically lower in the intervention group, with an HR of 0.91 (95% CI, 0.83–1.01).[152] There was no difference in all-cause mortality, overall mortality, or the incidence of cardiovascular events.[153]
With regard to fruit and vegetable intake, a pooled analysis of eight cohort studies including more than 350,000 women with 7,377 incident breast cancers showed little or no association for various assumed statistical models.[154]
The Women's Healthy Eating and Living Randomized Trial [155] examined the effect of diet on the incidence of new primary breast cancers in women previously diagnosed with breast cancer. More than 3,000 women were enrolled and randomly assigned to an intense regimen of increased fruit and vegetable intake, increased fiber intake, and decreased fat intake, or a comparison group receiving printed materials on the “5-A-Day” dietary guidelines. After a mean of 7.3 years of follow-up, there was no reduction in new primary cancers, no difference in disease-free survival, and no difference in overall survival.
A randomized trial in Spain [156] assigned participants who were at high cardiovascular risk to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control Mediterranean diet (counseling to reduce dietary fat). The investigators reported a statistically significant reduction in major cardiovascular events, which was the trial’s primary endpoint.[157] The investigators also addressed other endpoints, including the incidence of breast cancer, although it is not specified how many were examined. Based on only 35 cases of invasive breast cancer (as compared with 288 major cardiovascular events), the respective rates of breast cancer were 8 of 1,476 (0.54%); 10 of 1,285 (0.78%); and 17 of 1,391 (1.22%) with respective average follow-up durations of 4.8, 4.3, and 4.2 years. The circumstances of the study make it difficult to determine the statistical significance of these differences.

Vitamins

The potential role of specific micronutrients for breast cancer risk reduction has been examined in clinical trials, with cardiovascular disease and cancer as outcomes. The Women’s Health Study, a randomized trial with 39,876 women, found no difference in breast cancer incidence at 2 years between women assigned to take either beta carotene or placebo.[158] In this same study, no overall effect on cancer was seen in women taking 600 IU of vitamin E every other day.[159] The Women’s Antioxidant Cardiovascular Study examined 8,171 women for incidence of total cancer and invasive breast cancer and found no effect for vitamin C, vitamin E, or beta carotene.[160] Two years later, a subset of 5,442 women were randomly assigned to take 1.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12, or placebo. After 7.3 years, there was no difference in the incidence of total invasive cancer or invasive breast cancer.[161]
Fenretinide [162] is a vitamin A analog that has been shown to reduce breast carcinogenesis in preclinical studies. A phase III Italian trial compared the efficacy of a 5-year intervention with fenretinide versus no treatment in 2,972 women, aged 30 to 70 years, with surgically removed stage I breast cancer or DCIS. At a median observation time of 97 months, there were no statistically significant differences in the occurrence of contralateral breast cancer (P = .642), ipsilateral breast cancer (P = .177), incidence of distant metastases, nonbreast malignancies, and all-cause mortality.[163]

Active and passive cigarette smoking

The potential role of active cigarette smoking in the etiology of breast cancer has been studied for more than three decades, with no clear-cut evidence of an association.[164] Since the mid-1990s, studies of cigarette smoking and breast cancer have more carefully accounted for secondhand smoke exposure.[164,165] A recent meta-analysis suggests that there is no overall association between passive smoking and breast cancer and that study methodology (ascertainment of exposure after breast cancer diagnosis) may be responsible for the apparent risk associations seen in some studies.[166]

Underarm deodorants/antiperspirants

Despite warnings to women in lay publications that underarm deodorants and antiperspirants cause breast cancer, there is no evidence to support these concerns. A study based on interviews with 813 women who had breast cancer and 793 controls found no association between the risk of breast cancer and the use of antiperspirants, the use of deodorants, or the use of blade razors before these products were applied.[167] In contrast, a study of 437 breast cancer survivors found that women who used antiperspirants/deodorants and shaved their underarms more frequently had cancer diagnosed at a significantly younger age. A possible explanation for this finding is that these women had an earlier menarche or higher levels of endogenous hormones, both known to be risk factors for breast cancer and to increase body hair.[168]

Statins

Two well-conducted meta-analyses of RCTs [169] and RCTs plus observational studies [170] found no evidence that statin use either increases or decreases the risk of breast cancer.

Bisphosphonates

Oral and intravenous bisphosphonates for the treatment of hypercalcemia and osteoporosis have been studied for a possible beneficial effect on breast cancer prevention. Initial observational studies suggested that women who used these drugs for durations of approximately 1 to 4 years had a lower incidence of breast cancer.[171-174] These findings are confounded by the fact that women with osteoporosis have lower breast cancer risk than those with normal bone density. Additional evidence came from studies of women with a breast cancer diagnosis; the use of these drugs was associated with fewer new contralateral cancers.[175] With this background, two large randomized placebo-controlled trials were done. The Fracture Intervention Trial (FIT) treated 6,194 postmenopausal osteopenic women with either alendronate or placebo and found no difference at 3.8 years in breast cancer incidence, with incidence of 1.8% and 1.5%, respectively (HR, 1.24; CI, 0.84–1.83). The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PRT) examined 7,580 postmenopausal osteoporotic women with either intravenous zoledronate or placebo and found no difference at 2.8 years in breast cancer incidence, with incidence of 0.8% and 0.9%, respectively (HR, 1.15; CI, 0.7–1.89).[176]

Working night shifts

In 2007, the World Health Organization’s International Agency for Research on Cancer (IARC) classified shift work that involves circadian disruption as a probable breast carcinogen. The principal evidence was from animal studies. There was limited evidence from human studies at the time.[177] In 2013, a meta-analysis of 15 epidemiologic studies concluded that there was weak evidence of an increased incidence of breast cancer among women who had ever worked night shifts.[178] In 2016, the results from three recent prospective studies from the United Kingdom, involving nearly 800,000 women, were combined with results from seven other prospective studies and showed no evidence of any association between breast cancer incidence and night shift work. In particular, the confidence intervals for the incidence rate ratios were narrow, even for 20 years or more of night shift work (rate ratio, 1.01; 95% CI, 0.93–1.10). These results exclude a moderate association of breast cancer incidence with long duration of night shift work.[179]
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