Breast cancer risk for

The Nurses Health Study is characterized as generating much confusion and misinformation (Campbell, 2005, p. 272fT). This critique is directed mostly toward the Nurses Health Study findings that dietary (animal) fat and fiber did not relate to breast cancer risk. For still other criticisms of ihe nurses study, consult Chapter 14 of the book. 

Carotenoids and breast cancer — Among seven case-control studies investigating the correlation between different carotenoid plasma levels or dietary intakes and breast cancer risk, five showed significant inverse associations with some carotenoids. - In most cases, this protective effect was due to 3-carotene and lutein. However, one (the Canadian National Breast Screening Study ) showed no association for all studied carotenoids including (I-carotene and lutein. More recently, another study even demonstrated a positive correlation between breast cancer risk and tissue and serum levels of P-carotenes and total carotenes. Nevertheless, these observational results must be confirmed by intervention studies to prove consistent. 

CD Since the publication of the Women s Health Initiative study, there has been an increase in the use of non-hormonal therapies for the management of menopausal symptoms. Particularly for women with CHD and breast cancer risk factors, non-hormonal therapies may offer an alternative to assist with symptom management. A wide range of therapies, both prescription and herbal, have been studied with varying degrees of success. In choosing a particular therapy, it is important to match patient symptoms with a therapy that is not only effective but also safe. 

HRT is indicated primarily for the relief of moderate to severe vasomotor symptoms. It remains the most effective treatment for vasomotor symptoms and should be considered only in women experiencing those symptoms. Women with mild vasomotor symptoms may benefit from nonpharmacologic therapy alone however, many women will seek medical treatment for these symptoms. The benefits of HRT outweigh the risks in women who do not have CHD or CHD and breast cancer risk factors however, careful consideration should be given to alternative therapies for the relief of menopausal symptoms in women with these risks. Women should be involved in the decision and may choose to use HRT despite having some risk factors owing to the severity of their symptoms. Regardless of the situation, HRT should be prescribed at the lowest dose that relieves or reduces menopausal symptoms and should be recommended only for short-term use. Women should be reassessed every 6 to 12 months, and discontinuation of therapy should be considered. 

Breast cancer is the most common cancer in women in the United States. Observational data indicated an association between HRT and breast cancer risk. The WHI was the first RCT to demonstrate an increased risk of invasive breast cancer among women taking HRT. In fact, the trial was stopped early owing to an increased incidence of breast cancer in women taking HRT (0.38%) compared with placebo (0.3%) (HR 1.26, 95% Cl 1-1.59). This translates into an NNTH of 1250 and 8 more cases of invasive breast cancer for every... 

Long-term use of hormone-replacement therapy and concurrent use of progestins appear to contribute to breast cancer risk.7 The use of postmenopausal estrogen-replacement therapy in women with a history of breast cancer generally is considered contraindicated. However, most experts believe that the safety and benefits of low-dose oral contraceptives currently outweigh the potential risks and that changes in the prescribing practice for the use of oral contraceptives are not warranted. Oral contraceptives are known to reduce the risk of ovarian cancer by about 40% and the risk of endometrial cancer by about 60%. 

A number of calculators are available on the Internet to estimate a patient s risk of developing breast cancer. The National Cancer Institute (NCI) has an online version of the Breast Cancer Risk Assessment Tool that is considered to be the most authoritative and accurate standard (www.cancer.gov/ bcrisk-tool). The Breast Cancer Risk Assessment Tool was designed for health professionals to project a women s individualized risk for invasive breast cancer over a 5-year period and over her lifetime. 

In 1990, Vatten et al.51 in Norway subsequently reviewed data on breast cancer risk from a cohort of 14,593 women with 152 cases of breast cancer during a follow up of 12 years on subjects who were between 35 and 51 years old at the beginning of the study and between 46 and 63 years at the end. They reported no overall statistically significant correlation between breast cancer and coffee consumption, but when body mass index was taken into account, lean women who consumed >5 cups per day had a lower risk than women who drank two cups or less. In obese women, however, there was a positive correlation between coffee intake and breast cancer. In a 1993 study, though, Folsom and associates52 failed to find an association between caffeine and postmenopausal breast cancer in 34,388 women in the Iowa Women s Health Study, with a median caffeine intake of 212 mg/day in women who developed breast cancer and 201 mg/day for women who did not and in Denmark, Ewertz53 studied... 

The Million Women Study reported that current use of hormone therapy increased breast cancer risk and breast cancer mortality. Increased incidence was observed for estrogen only, estrogen plus progestogen, and for tibolone. 

In this chapter we will review the basic aspects of endocrine regulation of breast tissue growth and development. The relationship between genetics, estrogen exposure, and breast cancer risk will be discussed, and preclinical and clinical experience in the use of SERMS for both prevention and adjuvant treatment of ER-positive breast cancer will be reviewed and put in perspective. 

Three other studies were conducted to investigate the preventive potential of tamoxifen. One in Italy (Veronesi et al. 1998), one at the Royal Marsden Hospital, United Kingdom (Powles et al. 1998), and a multicentric international study (IBIS 2002). The British study was the smallest in size (2471 participants) but concentrated on women with a high incidence of family history and consequently presented a higher number of breast cancers. The Italian trial included only women with previous hysterectomy and, accordingly, around 50% had also undergone bilateral oophorectomy. The family risk was low only 15% had a first-degree relative affected by breast cancer. Both European studies permitted concurrent HRT, and 26% of the participants in the British trial received HRT while on study and 42% had ever received HT for menopausal symptoms. Neither of the studies showed any positive effect of the treatment with tamoxifen on the incidence of breast cancer. Reasons for this lack of effect can be different for each trial. 

As previously mentioned, HT is considered to increase risk for invasive breast cancer. The ability of raloxifene to reduce breast cancer risk was evaluted after MORE (Lippman 2001 Johnell et al. 2004) and has been evaluated recently with a consideration of all the breast cancer cases diagnosed after MORE + CORE (Purdie et al. 2004). Previous HT use was reported by 2235 women and no previous HT use by 5447 women. In these women, the overall reduction in invasive breast cancer incidence for the 8 years of MORE plus CORE was 66% (HR = 0.34 95% Cl = 0.22-0.50). In the placebo group the incidence of invasive breast cancer was 2.7% in those with prior HT use compared to 2.1% in those with no prior use (p = 0.279). In women with a history of prior HT use, raloxifene significantly reduced invasive breast cancer incidence by 71% (HR = 0.29 95% Cl = 0.14-0.59) compared to placebo. In women with no prior exposure to HT, a 64% reduction in incidence of invasive breast cancer was found in those receiving raloxifeneX (HR = 0.36 95% Cl = 0.22-0.59). The magnitude of risk reduction with raloxifene did not differ irrespective of the previous exposure to HT (interaction p = 0.618). 

Chlebowski RT, Col N, Winer EP et al. (2002) American Society of Clinical Oncology Technology assessment of pharmacologic interventions for breast cancer risk reduction including tamoxifen, raloxifene, and aromatase inhibition. J Clin Oncol 20(15) 3328—3343... 

The observation that women with breast cancer receiving tamoxifen had a reduced incidence of contralateral cancer was the basis for the NSABP-PI study, a randomized, double-blind, placebo-controlled trial that began in 1992. The main objective was to ascertain whether tamoxifen might effectively reduce the risk for breast cancer in women with a high risk of developing this disease. A total of 13,388 women > 35 years old were randomized to either tamoxifen (20 mg/d) or placebo for 5 years. In 1998, the trial was prematurely interrupted as the hypothesis of the study was confirmed (Fisher et al. 1998). However, the reduction in breast cancer risk with tamoxifen was accompanied by an increase in the incidence of invasive endometrial cancer (mean RR = 2.53). The increased risk was seen principally among women > 50 years old with a RR of 4.01, while among women < 49 years old the RR was 1.21. 

A woman s lifetime risk of breast cancer is approximately 1 in 8, Breast cancer clusters in families the risk of breast cancer doubles for a woman with one affected first-degree relative (e.g., mother, sister, or daughter). The risk increases further if there are multiple affected relatives or if the relatives developed early-onset breast cancer. 

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